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I F Pollack

Publications and source records attributed to I F Pollack.

104 records · Page 6Linked to original sources
PubMed1990

Patterns of immune rejection of mouse neocortex transplanted into neonatal rat brain, and effects of host immunosuppression.

We studied the histological and immunological characteristics of graft rejection in the rodent central nervous system (CNS) using embryonic mouse neocortex transplanted into the CNS of neonatal rats. Grafts from animals aged 8-145 days (n = 210) were examined using standard histological techniques for demonstrating cell morphology and fiber projections. Immunohistochemical techniques were used to identify graft projections into the host CNS. The incidence of graft rejection was 18% for animals between 18 and 30 days of age, but increased abruptly to 73% for animals older than 30 days. No graft rejection was seen in animals younger than 18 days. In a smaller group of xenograft recipient rats sacrificed at specific time points before and after one month of age, detailed immunohistochemical studies were performed to correlate the histological appearance of the graft with the level of major histocompatibility complex (MHC) class I and II immunoreactivity, and microglial, astrocytic and lymphocytic staining within the graft and host brain. Evidence of mild rejection as manifested by the appearance of scattered lymphocytes within the graft coincided with the development of Class I and II immunoreactivity within the graft and at the graft-host interface, which was demonstrated in some animals as early as 24 days. At 29 days of age, rejecting grafts showed diffuse MHC expression within the graft and at the graft-host interface; in contrast, unrejected grafts failed to show MHC immunoreactivity. Thirty-four day-old grafts often showed severe rejection with perivascular lymphocytic cuffing within the graft and in host parenchyma remote from the graft associated with increased MHC immunoreactivity within the host brain. In grafts older than 34 days there was frequently a violent rejection reaction with disruption of the cytoarchitecture of the graft and surrounding host tissues, and widespread MHC antigen expression. Immunosuppression with cyclosporin A was effective in avoiding rejection. The high incidence of rejection with neocortical xenografts is in striking contrast to the much lower incidence seen with retinal xenografts. This suggests that there are immunological features unique to neocortex which incite host recognition and rejection.

Animals↗
PubMed1990

The blood-brain barrier protects foreign antigens in the brain from immune attack.

To examine the role of the blood-brain barrier (BBB) in maintaining immune privilege in the brain, the BBB in the region of stably integrated mouse neural grafts implanted in neonatal rat brains was transiently disrupted by intracarotid infusion of hypertonic mannitol. This led to graft rejection and to prominent expression of major histocompatibility complex (MHC) antigens on cells adjacent to the graft. Grafts in control animals receiving an intracarotid infusion of isotonic saline showed only rare MHC expression and no increased incidence of rejection. Opening the barrier in the absence of a graft caused neither MHC expression nor cellular infiltration within the brain, suggesting that the effects of the hypertonic infusion were not produced by an indirect injury-mediated effect on the host brain. We conclude that the integrity of the blood-brain barrier is an important factor in the relative immune privilege of nonsyngeneic neural grafts.

Animals↗
PubMed1990

Response of malignant glioma cell lines to activation and inhibition of protein kinase C-mediated pathways.

To evaluate the role of protein kinase C-mediated pathways in the proliferation of malignant gliomas, this study examined the effect of a protein kinase C (PKC)-activating phorbol ester (12-O-tetradecanoyl-13-phorbol acetate or TPA) and a protein kinase C inhibitor (polymyxin B) on deoxyribonucleic acid (DNA) synthesis of malignant glioma cells in vitro. A serum-free chemically defined medium, MCDB 105, was employed for all studies. Two established human malignant glioma cell lines (T98G and U138), two rat glioma lines (9L and C6), and two low-passage human glioma lines (obtained from surgical specimens) were studied. With the exception of the C6 line, all tumors responded in a dose-dependent fashion to nanomolar concentrations of TPA with a median effective dose that varied from 0.5 ng/ml for the U138 glioma to 1 ng/ml for the T98G glioma. At optimal concentrations (5 to 10 ng/ml), TPA produced a two- to five-fold increase in the rate of DNA synthesis (p less than 0.05) as assessed by incorporation of 3H-thymidine. However, TPA had no additive effect on the mitogenic response produced by epidermal growth factor (EGF) or platelet-derived growth factor (PDGF). Inhibition of PKC using the antibiotic polymyxin B (20 micrograms/ml) abolished the TPA-induced mitogenic response in the five responsive lines tested. In two tumors (U138 and 9L), polymyxin B also eliminated EGF-, PDGF-, and serum-induced DNA synthesis as well as abolishing baseline DNA synthesis. These cells remained viable, however, as assessed by trypan blue exclusion; after removal of polymyxin B from the medium, they were able to resume DNA synthesis in response to TPA and serum. In the three other tumors (T98G and the two low-passage human glioma lines), growth factor-induced and serum-induced DNA synthesis were inhibited by approximately 25% to 85%. It is concluded that PKC-mediated pathways affect DNA synthesis in the human malignant glial tumors studied. The response of the glioma cells to TPA is similar to the responses seen in fetal astrocytes, but differs significantly from those reported for normal adult glial cultures. Because the response of the 9L glioma to TPA is similar to the responses seen in the human tumors, the 9L rat glioma model may prove useful for examining the role of PKC-mediated pathways in controlling glioma growth in vivo.

Animals↗
PubMed1990

Response of malignant glioma cell lines to epidermal growth factor and platelet-derived growth factor in a serum-free medium.

The use of a serum-free culture system for assessing the growth factor responsiveness of malignant glial cells is described. The mitogenic properties of epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were examined in three human malignant glioma cell lines (T98G, U87, and U138). Each of the three had high-affinity EGF receptors and all responded in a dose-dependent fashion to physiological concentrations of EGF. These cell lines also showed a pronounced mitogenic response to PDGF which equaled or exceeded that achieved with EGF. Simultaneous stimulation with both factors produced an additive response, which approximated that obtained in medium supplemented with 10% fetal calf serum. The authors conclude that functional EGF and PDGF receptors were present in the human malignant glial tumors studied. The response of the human glioma lines to these growth factors in many respects parallels the response seen in fetal astrocytes tested under similar conditions. In contrast, the behavior of two chemically induced rat gliomas (9L and C6) differed significantly from that seen in the human lines, suggesting that the rat lines may not be entirely acceptable as models for studying the growth characteristics of human malignant glial tumors.

Brain Neoplasms↗
PubMed1989

Prognostic factors in the diagnosis and treatment of primary central nervous system lymphoma.

The authors describe the results of multimodality therapy in 27 patients with biopsy-proven primary central nervous system (CNS) lymphoma treated between 1976 and 1986. Treatment included surgical resection (15 patients), radiotherapy (27 patients), and chemotherapy (nine patients). Actuarial survival rates for the 27 patients at 1, 2, and 5 years after diagnosis were 70%, 54%, and 45%, respectively. Nine patients were recurrence-free at 8 to 106 months follow-up. A multivariate risk analysis identified five factors which had a favorable impact on survival: (1) age less than 60 years (P less than 0.02); (2) preoperative Karnofsky performance score greater than or equal to 70 (P less than 0.02); (3) presence of strictly hemispheric tumor (P less than 0.0003); (4) whole-brain radiation dose between 4000 and 5000 cGy (P less than 0.05); and (5) addition of chemotherapy to radiotherapy (P less than 0.002). Patients with complete tumor resolution on computed tomography 6 months after beginning treatment also had longer survival (P less than 0.01). The presence of malignant cells on cerebrospinal fluid cytologic examination correlated with an increased risk of distant metastasis (P less than 0.05). In those patients whose disease eventually recurred, the administration of an additional therapeutic modality significantly increased the length of postrecurrence survival (P less than 0.05). Although surgical resection provided no increase in survival, the addition of chemotherapy to postoperative cranial irradiation significantly enhanced the duration of survival. Our experience suggests that pretreatment clinical and diagnostic factors can help in predicting survival and in planning treatment.

Adult↗
PubMed1989

Spinal cord injury without radiographic abnormality in children--the SCIWORA syndrome.

Spinal cord injury in children frequently occurs without fracture or dislocation. The clinical profiles of 55 children with spinal cord injury without radiographic abnormalities (SCIWORA) are reported in detail to illustrate features of this syndrome. No patient had vertebral fracture or dislocation on plain films and tomographies. There were ten upper cervical (C1-C4), 33 lower cervical (C5-C8), and 12 thoracic cord injuries; of these, 22 were complete or severe lesions and 33 were mild lesions. The mechanism of the neural injury probably relates to the inherent elasticity of the juvenile spine, which permits self-reducing but significant intersegmental displacements when subjected to flexion, extension, and distraction forces. The spinal cord is therefore vulnerable to injury even though the vertebral column is spared from disruption, and this vulnerability is most evident in children younger than 8 years. All but one of the 22 children with profound neurologic injuries were younger than 8 years (p less than 0.000001), whereas 24 of 33 children with mild injuries were older. Younger children were also more likely to have severe upper cervical lesions (p less than 0.05); lower cervical lesions were distributed evenly through the ages of 6 months to 16 years. Thoracic injuries most commonly resulted from distraction or crushing. Distraction invariably involved violent forces, and crush injuries were usually caused by children being run over while lying prone, when the spinal column was acutely bowed towards the spongy abdominal and thoracic cavities. Fifteen children had delayed onset of neurologic deficits; nine of these had transient warning symptoms of paresthesia, subjective paralysis, and Lhermitte's phenomenon 30 minutes to 4 days before the onset of deterioration. Eight other children suffered a second SCIWORA 3 days to 10 weeks after the initial SCIWORA. The spines in these children were presumably rendered incipiently unstable by the initial injury and thus were susceptible to additional, often more severe, neurologic trauma. The long-term neurologic outcome in children with SCIWORA is solely determined by their admission neurologic status. Realistically, the outcome can thus only be improved by: 1) ruling out occult fractures and subluxation which will require surgical fusion; 2) identifying patients likely to have delayed deterioration; and 3) preventing recurrent SCIWORA. Our experience and recommendations in these regards are discussed.

Adolescent↗
PubMed1989

Neurilemomas of the trigeminal nerve.

Sixteen patients with trigeminal neurilemoma have been treated at the University Health Center of Pittsburgh during the last 15 years. Two patients had middle fossa tumors arising from the trigeminal ganglion, four had posterior fossa tumors arising from the trigeminal roots, six had "hourglass" lesions extending above and below the tentorium and involving the trigeminal ganglion and its roots, and four had tumors arising from the trigeminal branches and extending through the superior orbital fissure, foramen rotundum, or foramen ovale. In seven patients, tumor had also invaded the cavernous sinus. The clinical and radiographic features of these tumors, the operative approaches employed, and the postoperative outcome are discussed. Complete tumor excision was achieved in 12 patients; all 12 remain free of recurrence 3 to 157 months after surgery. In contrast, all four patients who underwent subtotal tumor excision showed progressive neurological deterioration from regrowth of residual tumor within 3 years of the initial surgery. Two of these four subsequently had total tumor excision and both are disease-free 23 and 34 months after the second procedure. Major morbidity developed in only one of the 16 patients. There were no operative deaths. Nine patients had preserved or improved trigeminal function after treatment.

Cranial Nerve Neoplasms↗
PubMed1988

Stereotaxic intracavitary irradiation for cystic craniopharyngiomas.

Stereotaxic intracavitary irradiation with instillation of phosphorus-32 (32P) colloidal chromic phosphate was performed in nine patients with cystic craniopharyngiomas. Serial neurological, ophthalmological, neuroendocrinological, and radiological examinations were performed before and after treatment. Dosimetry was determined based on a computerized tomography (CT) estimation of tumor volume, and was calculated to provide a tumoricidal dose (200 to 300 Gy) to the cyst wall. The follow-up period ranged from 14 to 45 months (mean 27 months). After treatment, all nine patients showed improvement of symptoms and radiological evidence of cyst regression. Because of an expanding solid component producing recurrent symptoms, one patient required a craniotomy 14 months after isotope instillation. Three of five patients with impaired visual acuity before surgery had significant improvement in acuity after treatment. Preoperative visual field defects in eight patients improved in four after 32P therapy. Of seven patients with preoperative endocrine abnormalities, one individual showed almost complete normalization and another had improvement in endocrine function. Patients who exhibited residual neuroendocrine function before isotope instillation developed no significant deterioration in endocrine status during the follow-up period. The findings suggest that stereotaxic intracavitary irradiation is a safe and effective treatment which should be considered as the initial surgery for cystic craniopharyngiomas.

Adolescent↗
PubMed1988

Bilateral trigeminal neuralgia: a 14-year experience with microvascular decompression.

Thirty-five patients with trigeminal neuralgia (TN) bilaterally underwent posterior fossa microvascular decompression (MVD) between 1971 and 1984. They comprised 5.0% of a larger series of 699 patients with TN who underwent MVD during that interval. Compared to the subgroup of 664 patients with only unilateral symptoms, the population with bilateral TN included a greater percentage of females (74% vs. 58%, p less than 0.1), a higher rate of "familial" TN (17% vs. 4.1%, p less than 0.001), and an increased incidence of additional cranial nerve dysfunction (17% vs. 6.6%, p less than 0.05) and hypertension (34% vs. 19%, p less than 0.05). Of the 35 patients with bilateral TN, 10 underwent bilateral MVD (22 procedures) and 25 underwent unilateral MVD (30 procedures). In the latter patients, pain on the nonoperative side was well controlled with medication alone or had previously been treated by ablative procedures. Good or excellent pain control was achieved after one MVD was performed in 40 of the 45 sides treated (89%), and was maintained 1, 5, and 10 years after surgery in 82%, 66%, and 60%, respectively, based on life-table analysis. Six of 10 patients with recurrent symptoms underwent repeat unilateral MVD. Good or excellent long-term pain control was maintained in all six. With these repeat procedures included, symptom control at 1, 5, and 10 years after initial surgery was maintained in 87%, 78%, and 78% of the treated sides, respectively. Overall, 26 of 35 patients (74%) maintained good or excellent pain relief throughout the duration of the study (mean follow-up period 75 months) without resumption of regular medication usage. Although preoperative neurological deficits resulting from previous ablative procedures were seen in the majority of patients before MVD, no patient developed new major trigeminal sensory loss or masseter weakness after MVD. Operative mortality was zero. The results indicate that posterior fossa MVD is an effective and relatively safe treatment for the majority of patients with bilateral "idiopathic" TN, avoiding the risks of bilateral trigeminal nerve injury seen with other approaches.

Cerebellopontine Angle↗
PubMed1988

Recurrent spinal cord injury without radiographic abnormalities in children.

Spinal cord injury without radiographic abnormality is a well-known entity in the pediatric age group. Age-related elasticity of the vertebral ligaments as well as immaturity of the osseous structures in the pediatric spine allow momentary subluxation in response to deforming forces. The resultant neurological injuries range from transient dorsal column dysfunction to complete cord transection. Between 1960 and 1985, 42 such injuries were treated at the Children's Hospital of Pittsburgh. Management of these radiographically occult spinal cord injuries consisted of cervical immobilization for 2 months in a hard collar and restriction of contact sports. Recurrent cord injury occurred in eight cases during the 2-month immobilization period. A clearly defined traumatic episode was identified in seven of the eight patients, although in four children the recurrent trauma to the spine was trivial. Five of the children removed their collars briefly before the second injury, and two children incurred reinjury with the hard collar in place. The remaining child was too young for hard-collar immobilization, and recurrent neurological deterioration occurred during sleep. Serial flexion-extension films failed to detect frank instability in any of the eight cases. The children most susceptible to reinjury were those who sustained mild or transient neurological deficits from an initial cord injury and who rapidly resumed normal activities. Radiographically occult spinal instability resulting from the initial injury to the vertebral and paravertebral soft tissues presumably made these children vulnerable to recurrent spinal cord injury, often from otherwise insignificant trauma. During the last 21 months, 12 additional children have been managed with a more stringent protocol combining neck immobilization in a rigid cervical brace for 3 months and restriction of both contact and noncontact sports, together with a major emphasis on patient compliance. With this new protocol, no recurrent cord injuries have been documented.

Adolescent↗
PubMed1987

Chronic granulomatous disease with cranial fungal osteomyelitis and epidural abscess. Case report.

A patient is described with osteomyelitis of the cranium and epidural abscess due to Aspergillus fumigatus as the presenting manifestations of chronic granulomatous disease. The diagnosis was suggested by the unusual nature of the organism isolated and confirmed by appropriate laboratory studies. The details of diagnostic assessment and therapeutic management are discussed, and the central nervous system manifestations of chronic granulomatous disease are reviewed.

Brain Abscess↗
PubMedDate not supplied

Cerebellar astrocytomas in children.

Cerebellar astrocytomas, as a group, carry a more favorable prognosis than most other brain tumors, because these neoplasms generally are histologically benign and amenable to extensive resection. However, it is clear that a number of factors have an impact on prognosis. In particular, resection extent has been strongly associated with progression-free survival: patients undergoing gross total resection appear to have a substantially better prognosis than those undergoing incomplete resection. Brainstem invasion, which is the factor that most often precludes a complete resection, has also been associated with a less favorable prognosis. In addition, histological features indicative of malignancy are clearly associated with a poor outcome. In contrast to the above observations, which have been established convincingly in the literature, a number of issues regarding cerebellar astrocytomas remain unresolved. First, the correlation between histology and prognosis among patients with low-grade cerebellar astrocytomas is uncertain: in some series, pilocytic astrocytomas have been associated with a better prognosis than non-pilocytic tumors, but in other studies, no such relationship has been observed. Second, the role of radiotherapy after incomplete resection of a low-grade cerebellar astrocytoma remains problematic. In view of the lack of convincing data in this regard, many groups, including our own, defer radiotherapy until there is evidence of progressive disease that is surgically unresectable. Finally, the frequency of follow-up in patients with cerebellar astrocytomas remains largely empirical. Although most recurrences are detected within a few years after initial surgery, late recurrences are well known, which raises the question of when and if such patients should be regarded as "cured' of their disease. Long-term multi-institutional natural history studies are in progress to address the above issues.

Astrocytoma↗
PubMedDate not supplied

Special issues in the management of gliomas in children with neurofibromatosis 1.

Neurofibromatosis 1 (NF1) is a common multisystem disorder that is frequently associated with neoplastic and non-neoplastic lesions within the central nervous system. Improvements in neuroimaging have led to increased detection of both types of lesions. Focal areas of increased T2 signal represent the most common abnormalities detected. The vast majority of such lesions are non-neoplastic and fluctuate in number and size during childhood. Optic pathway tumors are second in frequency and generally manifest an indolent natural history, although some lesions will increase in size over time and lead to progressive visual impairment. A smaller percentage of patients will develop gliomas within the cerebral and cerebellar hemispheres of brain-stem. This article will review areas of controversy in the evaluation and follow-up of patients with NF1 and will present our approach to these issues. We will also discuss therapeutic considerations in these patients that take into account the unique features of the underlying disorder.

Brain Neoplasms↗