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Biomedical subjects

P C Burger

Publications and source records attributed to P C Burger.

At least 19 recordsLinked to original sources
PubMed1992

Macrophage markers in diagnostic neuropathology.

It can be difficult to differentiate the cells of infiltrating gliomas from macrophages associated with demyelinating lesions or cerebral infarcts, especially in tissue with freezing artifact or tissue that is technically suboptimal. We therefore sought to identify a reliable immunohistochemical marker for central nervous system macrophages that could be used on routinely processed tissue. The reactions of commercially available markers [Ham-56, Mac 387, CD68, CR3/43, DR alpha, lysozyme, CD16, and Ricinus communis agglutinin-1 (RCA-1)] were studied in normal cerebellum, subacute infarcts, viral encephalitis with microglial nodules, radiation necrosis, Alzheimer's disease, medulloblastoma, T-cell lymphoma, oligodendroglioma, gliomatosis cerebri, and microgliomatosis cerebri. We also performed a more extensive investigation of Ham-56 with largely surgical material. We concluded that (a) RCA-1 is a sensitive marker for microglia, either resting or responding to injury, but staining must be interpreted carefully because endothelial cells and reactive astrocytes frequently stain as well. This marker was useful in highlighting focal inflammation in HIV encephalitis. (b) CD68 is a specific marker for resting microglia. A case of microgliomatosis cerebri was intensely stained. (c) Ham-56 is a sensitive, specific (with the exception of endothelial cells), and reliable marker of central nervous system macrophages in routinely processed autopsy and surgical material. It is especially useful in distinguishing the macrophages in demyelinating disease and cerebral infarcts from neoplastic glial cells.

Adolescent↗
PubMed1992

Rasmussen's encephalitis: neuroimaging findings in four patients.

Rasmussen's encephalitis is a devastating disease of childhood causing progressive neurologic deficits and intractable seizure activity. Patients frequently have episodes of epilepsia partialis continua and, much less frequently, generalized status epilepticus. The seizures are intractable despite aggressive medical management. In advanced cases, hemispherectomy appears to be the only option to control the seizures. Permanent physical and mental impairments are inevitable. The cause of this disease is unknown, although pathologic specimens demonstrate nonspecific changes that are compatible with viral encephalitis. The progressive brain damage is typically so insidious in onset and gradual in course that it is difficult to make an accurate diagnosis on the basis of clinical evidence. We retrospectively evaluated the CT, xenon CT, positron emission tomographic, and MR neuroimaging findings in four young patients with pathologically suspected Rasmussen's encephalitis (three patients had CT scans, two had xenon CT scans, two had MR scans, and one had a positron emission tomogram). All studies showed abnormalities of the involved cerebral hemisphere: CT and MR revealed nonspecific atrophy, xenon CT showed decreased cerebral blood flow, and positron emission tomography revealed a hypometabolic state. Rasmussen's encephalitis is a diagnosis of exclusion; however, the information obtained from neuroimaging studies in combination with the clinical course should suggest this disorder.

Adolescent↗
PubMed1992

A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma.

This Phase III trial tested the efficacy and safety of intra-arterial 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) for the treatment of newly resected malignant glioma, comparing intra-arterial BCNU and intravenous BCNU (200 mg/sq m every 8 weeks), each regimen without or with intravenous 5-fluorouracil (1 gm/sq m three times daily given 2 weeks after BCNU). All patients also received radiation therapy. A total of 505 patients were randomly assigned within the study. Fifty-seven patients were excluded, primarily because of neuropathology error, and the remaining 448 patients constituted the Valid Study Group. Of the total 505 patients, 190 patients could not receive intra-arterial BCNU and 315 patients were randomly assigned to receive intra-arterial (167 patients) and intravenous (148 patients) BCNU. Actuarial analysis (log-rank) demonstrated reduced survival for the intra-arterial group (p = 0.03). Serious toxicity was observed in the intra-arterial group; 16 patients (9.5%) developed irreversible encephalopathy with computerized tomography evidence of cerebral edema, and 26 patients (15.5%) developed visual loss ipsilateral to the infused carotid artery. Administration of 5-fluorouracil did not influence survival. The survival rate between the intravenous and the intra-arterial BCNU patients with glioblastoma multiforme did not differ, but was worse for intra-arterial BCNU patients with anaplastic astrocytoma than for those receiving intravenous BCNU (p = 0.002). Neuropathologically, intra-arterial BCNU produced white matter necrosis. It is concluded that intra-arterial BCNU is neither safe nor effective in prolonging survival when administered by the methods used in this study of newly diagnosed patients with malignant glioma.

Adolescent↗
PubMed1991

Hyperfractionated radiation therapy in brain stem tumors. Results of treatment at the 7020 cGy dose level of Pediatric Oncology Group study #8495.

Between May 1986 and February 1988, 57 patients were accrued to the second dose level of a Phase I/II Pediatric Oncology Group (POG) study exploring the use of hyperfractionated radiation therapy (HRT) in children with high-risk brain stem tumors. Local fields were treated with fraction sizes of 117 cGy given twice daily, with a minimum interfraction interval of 6 hours, to a total dose of 7020 cGy in 60 fractions over 6 weeks. Information regarding clinical status during HRT was available for 55 patients (44 [80%] improved, 6 remained stable, and 5 deteriorated). Results of initial and follow-up computed tomography (CT) scan and/or magnetic resonance imaging (MRI) were available for review for 52 patients. One patient had a complete response (CR) to treatment, 3 had a partial response (PR) (more than 50% response), and 40 remained stable, for a total response rate (CR + PR + stable) of 77%. Median time to disease progression was 6 months. Median survival time was 10 months. Survival rate was 39.6% (standard error [SE] = 6.6%) at 1 year and 23% (SE = 5.8%) at 2 years. Complications of treatment included an enhanced skin reaction in six patients and otitis media and/or externa in nine. One patient bled into tumor shortly after completion of HRT, and three had intralesional necrosis. Five patients continued taking steroids for protracted periods in the face of improved clinical and/or radiologic findings. Complications related to the use of steroids included opportunistic infections, impaired glucose tolerance, hypertension, osteoporosis, and significant mood changes. In no patient was there evidence of any late injury attributable to HRT. When compared with results of treatment with HRT at a lower dose level (6600 cGy), there appears to be a trend toward improved survival at 7020 cGy despite a less favorable patient population at the higher dose level. A second dose escalation to 7560 cGy in 60 fractions over 6 weeks has been implemented as planned.

Adolescent↗
PubMed1991

Identification of early recurrence of primary central nervous system tumors by [18F]fluorodeoxyglucose positron emission tomography.

As aggressive neurosurgery and adjuvant therapy have become standard care for most patients with primary central nervous system (CNS) tumors, limitations of posttreatment neuroimaging techniques have become more apparent. Interpretation of computed cranial tomography (CT) and magnetic resonance imaging (MRI) in patients with brain tumors is complicated by changes related to surgery, corticosteroids, radiation, and chemotherapy. We investigated the role of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (FDG-PET) in these difficult diagnostic situations by obtaining FDG-PET scans in 5 patients following temporal lobectomy for epilepsy, in 5 patients with recurrent anaplastic gliomas before and after corticosteroid therapy, and in 5 patients after the development of histologically confirmed radionecrosis. We also obtained postoperative FDG-PET scans in 32 consecutive patients undergoing initial resection of a primary brain tumor. Our results indicate that glucose uptake as detected by FDG-PET scanning with [18F]fluorodeoxyglucose is not increased in the postoperative period; is not affected by steroid therapy; and accurately predicts early recurrence of tumor, supplementing other predictors of tumor behavior, including extent of resection, histological diagnosis, and postoperative CT. Thus PET using [18F]fluorodeoxyglucose can contribute to the optimum management of patients with primary brain tumors.

Adult↗
PubMed1991

Osteoblastic metastases from astrocytomas: a report of two cases.

The spread of primary central nervous system (CNS) neoplasms beyond the confines of the neuraxis is a relatively uncommon observation. Extraneural metastases involving bone are quite rare, and have been observed almost exclusively in cases of medulloblastoma, high-grade (III-IV) astrocytoma, and glioblastoma multiforme. To date there has been only one case reported of bone metastasis from a "well-differentiated" astrocytoma. We now report two cases of astrocytoma in children with diffuse osteoblastic metastases and a fulminant clinical course. These cases demonstrate that due to the potential morphologic heterogeneity of these neoplasms, an initial biopsy diagnosis of low-grade astrocytoma does not always imply a benign clinical course.

Adolescent↗
PubMed1991

"Desmoplastic" versus "classic" medulloblastoma: comparison of DNA content, histopathology and differentiation.

A microfluorometric analysis was performed to analyse the DNA content of 42 medulloblastomas (MBs) and to seek correlations, if any existed, between the DNA distribution and ploidy values, neoplasm types (i.e. classic vs desmoplastic), histological features of aggressiveness, and immunocytochemical features indicating glial and/or neuronal differentiation. Thirty-one cases were classified as classic and 11 cases as desmoplastic MBs. Ten of 11 desmoplastic MBs had a near-diploid main mode and the remaining 1 case had a near-tetraploid main mode. Moreover, 10 of 11 (90%) cases showed a "monomodal" DNA distribution diagram. All these cases showed a uniform histology. In contrast, classic MBs represented a heterogeneous group of neoplasms. Twenty-two cases were near-diploid, 5 cases were near-tetraploid and 3 cases were near-triploid. The histogram type distribution showed a similar heterogeneity. Twelve of 31 (39%) cases had a monomodal histogram, 12 (39%) cases had a bimodal diagram and 7 (22%) cases a complex DNA distribution. There was a statistically significant difference (P less than 0.001) in terms of prevalence of DNA monomodal histograms between classic and desmoplastic MBs. Significant correlations were not observed among classic MBs between histological features of aggressiveness, type and degree of differentiation and DNA distribution. The present study indicates that desmoplastic MBs represent a homogeneous group of neoplasms in terms of histology and DNA distribution. In contrast, classic MBs are lesions with different degrees of histologically apparent aggressiveness and a complex DNA distribution.

Adolescent↗
PubMed1991

Influence of the type of surgery on the histologic diagnosis in patients with anaplastic gliomas.

Stereotactic biopsy of CNS tumors provides a small amount of tissue for pathologic diagnosis. This potentially leads to inaccurate grading of gliomas because of their histologic heterogeneity. We compared histologic diagnoses in a consecutive series of 329 patients with newly diagnosed anaplastic gliomas whose diagnoses were established by either stereotactic biopsy or open resection. Of 262 patients undergoing resection, 214 (82%) had glioblastomas and 48 (18%) had anaplastic astrocytomas (AAs). Of 67 patients undergoing stereotactic biopsy, 33 (49%) had glioblastomas and 34 (51%) had AAs. This difference suggests that some AAs diagnosed by stereotactic biopsy are actually glioblastomas and has important implications for the design and interpretation of clinical trials.

Adult↗
PubMed1991

Interstitial chemotherapy with drug polymer implants for the treatment of recurrent gliomas.

Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I-II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks. Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself. The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy. Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.

Brain Neoplasms↗
PubMed1991

Progressive multifocal leukoencephalopathy. Diagnosis by in situ hybridization with a biotinylated JC virus DNA probe using an automated Histomatic Code-On slide stainer.

The accurate surgical pathological diagnosis of progressive multifocal leukoencephalopathy (PML) depends on the demonstration of pathognomonic histological features in cerebral biopsy tissue. The diagnosis may be difficult, however, if only small tissue fragments are submitted from the center of a demyelinating lesion. Previous studies by other authors have established that in situ hybridization with a biotinylated JC virus DNA probe can be a valuable diagnostic adjunct because it identifies the virally infected cells with great specificity and does not depend on the larger specimen, which may be necessary for a firm histological diagnosis. To confirm and extend these findings, we have used a commercially available biotinylated JC virus DNA probe to demonstrate the presence of viral DNA in formalin-fixed, paraffin-embedded tissues from four open biopsies, four needle biopsies, and two autopsies of patients with PML. With the goal of making this procedure applicable to the general surgical pathology laboratory, this method was adapted to the Histomatic Code-On slide stainer. The Histomatic is a programmable, robotic instrument with walk-away capability for hybridization histochemistry. Operation of this instrument requires the same expertise as execution of immunocytochemistry. With the advent of commercially available JC virus DNA probes and an automated system for hybridization histochemistry, this technology for diagnosis of PML may enter the routine diagnostic surgical pathology laboratory.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Pathology--trends and pitfalls in histologic diagnosis, immunopathology, and applications of oncogene research.

Classifications of pediatric neoplasms of the CNS are evolving from morphology-based approaches, that seek a "cell of origin" or "phase of embryogenesis," to more complicated and flexible systems that incorporate the results of immunohistochemical and molecular biology investigations. Markers of cellular proliferation are being employed as well. The development of improved classifications will depend on a reasoned application of newer methodologies to complement and, if necessary replace, the many worthy aspects of present classifications. Careful coordination among clinicians, radiologists, and pathologists is necessary to establish the clinical relevance of these findings. Application of these classifications and the techniques that make them possible will help resolve many current important issues. Among these are the validity of the PNET approach to embryonal tumors; the criteria for classification and grading of ependymomas; and the utility of subdividing cerebellar astrocytomas. Other important issues include the regional incidence and histologic prognostic features in pilocytic astrocytomas, the clinicopathologic features of well-differentiated neoplasms and hamartomatous lesions that are now being detected by magnetic resonance imaging, the utility of subclassification of medulloblastoma, and the status as an entity of the primitive polar spongioblastoma. The increasing familiarity of clinicians, radiologists, and pathologists with existing and "new" clinicopathologic entities will minimize the likelihood that well-differentiated, slowly growing, or well-circumscribed neoplasms are overgraded and treated by unnecessarily aggressive therapy. Pathologists also need to be aware that certain nonneoplastic lesions can be misconstrued as neoplasms.

Biomarkers, Tumor↗
PubMed1990

Oncogene amplification in pediatric brain tumors.

Despite a considerable amount of information concerning chromosomal and molecular abnormalities found in gliomas in adults, relatively little is known regarding these abnormalities in pediatric brain tumors. We have analyzed DNA from 37 primary brain tumors and 4 tumor-derived cell lines for oncogene amplification. Probes utilized represent 11 known oncogenes (erbB1, gli, neu, myc, L-myc, N-myc, H-ras, K-ras, N-ras, sis, and src). Of 20 primary medulloblastomas studied, only one tumor was found to have erbB1 amplification. In contrast, of the 4 medulloblastoma cell lines studied, 1 had c-myc amplification, 1 had erbB1 amplification, and 1 had amplification of N-myc. Twelve glial brain tumors were analyzed, and only 1 case with amplification of the erbB1 oncogene was found. Other tumors studied include 1 meningioma, 2 ependymomas, 1 anaplastic ependymoma, and 1 cerebral primitive neuroectodermal tumor, none of which had oncogene amplification. These results suggest that oncogene amplification is relatively uncommon in primary medulloblastomas, but the frequency and diversity of oncogene amplification is greater in tumors that can be established as cell lines. The lower frequency of erbB1 amplification in glial brain tumors in children compared to adults is consistent with the generally lower grade of glial tumor histology seen in pediatric patients. However, the case with amplification of the erbB1 oncogene represented 1 of 2 cases of glioblastoma multiforme we studied, which suggests that pediatric glioblastoma multiforme may have a similar frequency of erbB1 oncogene amplification to glioblastomas seen in adults. Our results suggest that oncogene amplification is a relatively uncommon mechanism of oncogene activation in pediatric brain tumors, and they provide molecular evidence for heterogeneity in tumors classified as medulloblastomas.

Blotting, Southern↗
PubMed1990

Barotrauma and air embolism in hyperbaric oxygen therapy.

A 69-year-old woman underwent hyperbaric oxygen therapy because of a nonhealing ulcer of her foot. During decompression, she developed a left-sided hemiplegia and confusion. Recompression resulted in transient neurologic improvement, but she eventually became comatose. Ventricular dysrhythmias developed and she died without regaining consciousness 17 h after onset of symptoms. An autopsy revealed diffuse interstitial pulmonary fibrosis with severe paracicatricial emphysema, chronic interstitial inflammation, and chronic bronchitis with abundant intrabronchial mucus. There was extensive multifocal ischemic injury of the cerebral cortex. The hippocampi, basal ganglia, and cerebellum were spared. Scattered acute myofiber necrosis was present in the heart. Clinical presentation and autopsy findings strongly support the diagnosis of air embolism and illustrate a potential risk of hyperbaric oxygen therapy in patients with preexisting pulmonary disease.

Aged↗
PubMed1990

Clinical and pathological analysis of spinal cord astrocytomas in children.

Twelve children with pathologically confirmed, well-differentiated spinal cord astrocytomas were studied, and correlations among the degree of resection, pathological characteristics, and time of recurrence were examined. Eight tumors were sampled for biopsy or subtotally resected, and 4 were thought to have been totally removed. Clinical recurrence was seen in 4 of 12 patients, 2 of whom died of their disease. The time to recurrence was 1, 2, 2, and 35 years, respectively. The other 8 children remain free of symptoms, with follow-up ranging from 6 months to 35 years (mean, 8.8 years). In 3 of 8 patients who underwent biopsy or subtotal resection, the tumor recurred, and 2 patients died, whereas there was one recurrence in the patients in whom a "total" resection had been obtained. The histologically well-differentiated nature of the lesions correlated well with the relatively prolonged clinical course seen in this series during the period of observation. The relatively long clinical courses seen in our limited series should be considered before high-risk therapy for spinal cord astrocytomas in children is implemented. The presence of four pilocytic astrocytomas in this group was of special interest, and it seems likely that these discrete neoplasms can be distinguished from the more infiltrating fibrillary astrocytic neoplasms by magnetic resonance imaging with enhancement with gadopentetate dimeglumine.

Adolescent↗
PubMed1990

MR imaging in patients with temporal lobe seizures: correlation of results with pathologic findings.

Thirty-nine consecutive patients with medically intractable complex partial seizures were studied with electroencephalography and MR imaging to localize an epileptogenic focus for temporal lobectomy. The patients were divided into three groups on the basis of pathologic findings after lobectomy: Group 1 comprised 13 patients with neoplasms, hamartomas, or cysts; group 2 comprised 13 patients with moderate and severe mesial temporal sclerosis (one patient was included in both groups 1 and 2); and group 3 comprised 14 patients who underwent aspiration lobectomy, which yielded limited tissue for pathologic study so no pathologic diagnosis was made. The majority of the patients in group 3 were assumed to have mesial temporal sclerosis. Abnormal MR signal in the temporal lobe on T2-weighted images was graded as minimal increase (1+), intermediate or moderate increase (2+), and very significant increase (3+). An abnormal signal was demonstrated in 26 (67%) of the 39 patients. In group 1, the tumor/cyst subgroup, an abnormal signal was seen in all 13 patients. Most had 3+ signal. There was increased signal in eight (62%) of 13 patients in group 2 and in six (43%) of 14 patients in group 3. This study suggests that MR can detect almost all tumors and a significant number of mesial temporal sclerosis lesions in individuals with complex partial seizures. On the basis of this small series, individuals who exhibit significant signal (3+) can be expected to have neoplasms, hamartomas, or cysts, and patients who exhibit minimal signal (1+) will usually have mesial temporal sclerosis.

Adult↗
PubMed1990

Value of sonography in the diagnosis of intracranial hemorrhage and periventricular leukomalacia: a postmortem study of 35 cases.

Periventricular leukomalacia and germinal matrix hemorrhages are major causes of neurodevelopmental abnormalities in the premature neonate. Although sonography is widely used to detect these abnormalities and is thought to be sensitive for hemorrhages and the later cystic stages of periventricular leukomalacia, its sensitivity for the more acute phase of periventricular leukomalacia remains to be determined. It has been difficult to study this issue because periventricular leukomalacia often is not lethal, and in postmortem studies there is usually a considerable interval between the time of in vivo imaging, if any, and the death of the patient. A "prospective" autopsy study was performed on brain specimens from infants who died at less than 1 year of age during a 10-month period. Thirty-five formalin-fixed brains were studied and sonographic images of these specimens were compared with histologic findings in whole brain sections to determine the sensitivity and specificity of sonography for the detection of germinal matrix hemorrhage and periventricular leukomalacia. Sonography identified germinal matrix hemorrhages as small as 5 mm, although smaller lesions were not visualized. Postmortem sonography had a sensitivity of 27% and specificity of 88% for all germinal matrix hemorrhages, but a sensitivity of 100% and specificity of 91% for hemorrhages larger than 5 mm. Periventricular leukomalacia, seen as hyperechoic areas in the periventricular white matter, was not detected as readily. For periventricular leukomalacia, the overall sensitivity and specificity were 50% and 87%, respectively. We conclude that sonography is useful for detecting the larger germinal matrix hemorrhages, but has more limited sensitivity in the early diagnosis of periventricular leukomalacia.

Cerebral Hemorrhage↗