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Biomedical subjects

G R Harsh

Publications and source records attributed to G R Harsh.

At least 37 records · Page 2Linked to original sources

Functional cerebral imaging in the evaluation and radiotherapeutic treatment planning of patients with malignant glioma.

PURPOSE: Functional magnetic resonance imaging (MRI) and positron emission tomography are relatively new modalities of great potential value in the evaluation, treatment, and subsequent follow-up care of patients with malignant glioma. We report our experience with the incorporation of functional imaging data into radiation therapy three-dimensional (3-D) treatment planning. METHODS AND MATERIALS: Over a 24-month period, a total of 37 positron emission tomography and 29 functional MRI studies have been conducted on eight consecutive patients prior to, during, and following the completion of radiation therapy. Functional imaging was conducted prior to radiation therapy treatment planning and at approximate 3-month follow-up time intervals. RESULTS: In two patients, functional imaging provided additional information over conventional imaging modalities and resulted in subsequent modification of conventional radiation therapy treatment planning. CONCLUSION: Although it is premature to make definitive statements regarding the use of these new imaging parameters in the prognostic setting, functional imaging may likely prove to be a useful adjunct in the initial evaluation, radiation treatment planning, and follow-up care of patients with malignant glioma.

Adult↗

A multi-institutional experience with stereotactic radiosurgery for solitary brain metastasis.

PURPOSE: A multi-institutional experience in radiosurgery for solitary brain metastases was combined to identify factors associated with safety, efficacy, tumor control, and survival. MATERIALS AND METHODS: A review of 116 patients with solitary brain metastases who underwent gamma knife stereotactic radiosurgery at five institutions was performed. The median follow-up was 7 months following radiosurgery and 12 months following diagnosis. Minimum tumor doses varied from 8-30 Gy (mean, 17.5 Gy). Forty-five patients failed prior radiotherapy and 71 had no prior brain irradiation. Fifty-one patients had radiosurgery alone and 65 underwent combined radiosurgery with fractionated large-field radiotherapy (mean dose, 33.8 Gy). RESULTS: Median survival was 11 months after radiosurgery and 20 months after diagnosis. Follow-up documented local tumor control in 99 patients (85%), tumor recurrence in 17 (15%), and documented radiation necrosis in one (1%). The 2-year actuarial tumor control rate was 67 +/- 8%. Tumor histology affected survival (better for breast cancer, p = .004) and local control (better for melanoma and renal cell, p = .0003) in multivariate analyses. Combined fractionated radiotherapy and radiosurgery improved local control (p = 0.111), but not survival in multivariate testing. CONCLUSION: Radiosurgery is effective in controlling solitary brain metastases with low morbidity. Further study is needed to better define optimum treatment parameters for radiosurgery.

Adult↗

Cerebral blood volume maps of gliomas: comparison with tumor grade and histologic findings.

PURPOSE: To assess the utility of magnetic resonance (MR) cerebral blood volume (CBV) maps in the evaluation of gliomas. MATERIALS AND METHODS: CBV maps from 19 patients with histologically proved gliomas were calculated from dynamic MR image sets acquired with echo-planar spin-echo imaging after intravenous injection of gadolinium-based contrast material. RESULTS: The maximum CBV varied from 0.82 to 5.40 in the high-grade group (n = 13) and from 1.01 to 1.21 in the low-grade group (n = 6). The difference was statistically significant. Maximum CBV was associated with mitotic activity and vascularity, but not with cellular atypia, endothelial proliferation, necrosis, or cellularity. CONCLUSION: MR CBV maps provided diagnostic information not available with conventional MR imaging in six cases and offers a functional parameter for assessing glioma grade and regions of focal activity.

Adult↗

Intramedullary hemorrhage in spinal cord hemangioblastoma. Report of two cases.

The authors describe two cases of intramedullary hemorrhage caused by thoracic hemangioblastoma. Both patients presented with acute paraplegia. The lesion in the first case was diagnosed by myelography and in the second by magnetic resonance imaging. Emergency surgical evacuation of the intramedullary hematoma and tumor was performed in these patients. Hemangioblastoma was confirmed by histopathological examination in both cases. Both patients remain paraplegic after 7 and 1 years, respectively. Intramedullary hemorrhage is a rare and devastating effect of spinal hemangioblastoma.

Adult↗

Stereotactic radiosurgery of cavernous sinus meningiomas as an addition or alternative to microsurgery.

To evaluate the response of cavernous sinus meningiomas to stereotactic radiosurgery, we reviewed our 54-month experience with 34 patients. All patients underwent radiosurgery with a 201-source cobalt-60 gamma unit. Twenty-eight patients (82%) had previous histological confirmation of a meningioma (1 to 5 cranial base craniotomies per patient); 6 (18%) were treated on the basis of neuroimaging criteria alone. The single-fraction radiation tumor margin dose (10 to 20 Gy) was designed to conform to the irregular tumor volumes in all patients. The maximum radiation dose to the optic nerve or tract was reduced to 9 Gy in 31 patients. No patient had tumor growth (100% tumor control) during the follow-up interval (median, 26 mo). Tumor regression was observed in 56% of patients imaged at an average of 18 months. Eight patients (24%) improved clinically at follow-up examinations. Four patients developed new or worsened cranial nerve deficits during the follow-up interval; two had subsequent full improvement. No patient developed an endocrinopathy or new extraocular muscle paresis. Stereotactic radiosurgery, using multiple isocenter dosimetry facilitated by the gamma unit, is an accurate, safe, and effective technique to prevent the growth of tumors involving the cavernous sinus. Despite the proximity of such tumors to adjacent cranial nerves, complications were rare. The maximum length of hospital stay was 36 hours, and all patients returned to their preoperative employment status within 3 to 5 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Bilateral temporal bone encephaloceles after cranial irradiation. Case report.

Irradiation of the central nervous system may cause significant morbidity, including endocrine dysfunction and intellectual impairment. The authors report a case of bilateral temporal bone encephaloceles in a 21-year-old man who had received prophylactic central nervous system irradiation for acute lymphocytic leukemia in early childhood. Endaural encephaloceles are uncommon, and most occur as a complication of mastoid surgery. The etiology, clinical features, radiological diagnosis, and surgical treatment of temporal bone encephaloceles are discussed.

Adult↗

Magnetic resonance imaging of tuberculum sellae meningiomas: preventing preoperative misdiagnosis as pituitary macroadenoma.

Despite recent advances in neurodiagnostic imaging, it may be difficult to differentiate tuberculum sellae meningiomas from pituitary macroadenomas preoperatively. Magnetic resonance (MR) imaging has supplanted computed tomography as the imaging modality of choice for sellar and parasellar lesions, but unenhanced MR imaging does not reliably distinguish between all tuberculum sellae meningiomas and pituitary macroadenomas. Accurate differentiation between these alternative diagnoses of a suprasellar mass is important because a tuberculum sellae meningioma always requires a craniotomy, whereas a transsphenoidal route is preferred for removing most pituitary macroadenomas. The gadolinium-enhanced MR images of seven patients with tuberculum sellae meningioma and seven with pituitary macroadenoma were reviewed retrospectively. Although no specific radiological feature was pathognomonic, a combination of several features allowed the correct diagnosis in all cases. Three characteristics of tuberculum sellae meningiomas distinguish them from pituitary macroadenomas: 1) bright homogeneous enhancement with gadolinium, as opposed to heterogeneous, relatively poor enhancement; 2) a suprasellar rather than a sellar epicenter of tumor; and 3) tapered extension of an intracranial dural base. Each of these findings can be subtle, but careful examination of gadolinium-enhanced, high-quality, thin section coronal and sagittal MR images of the parasellar region for this constellation of findings will allow the correct preoperative diagnosis in patients with either of these tumors.

Adenoma↗

The subtemporal, transcavernous, anterior transpetrosal approach to the upper brain stem and clivus.

The temporal lobe, posterolateral cavernous sinus, tentorium, and petrous apex restrict anterolateral surgical access to lesions of the upper brain stem and clivus. The authors describe a modified transpetrosal approach that enhances the exposure of clival chordomas and aneurysms of the basilar artery bifurcation. An intradural and extradural subtemporal approach is combined with division of the tentorium and superior petrosal sinus, posterolateral dissection of the cavernous sinus, and intradural removal of the petrous bone from its apex to the cochlea. The indications, advantages, and disadvantages of this subtemporal, transcavernous, anterior transpetrosal approach are described in detail, along with its use in six patients.

Adult↗

Unilateral hydrocephalus in adults.

The authors report 14 cases of unilateral hydrocephalus in adults. Headache was the most common presenting symptom. Unilateral hydrocephalus was documented in each patient with computed tomography scans; magnetic resonance imaging was also used in seven patients in the latter part of the series. Unilateral hydrocephalus was caused by tumor (seven patients), venous angioma (one patient), ependymal cyst (one patient), postinflammatory gliosis (one patient), and was idiopathic in four patients. The primary surgical treatment was craniotomy with fenestration of the septum pellucidum, which relieved symptoms in eight of nine patients for whom long-term follow-up data were available.

Adolescent↗

Von Hippel-Lindau disease and erythrocytosis: radioimmunoassay of erythropoietin in cyst fluid from a brainstem hemangioblastoma.

A 59-year-old woman with von Hippel-Lindau disease developed erythrocytosis and a recurrent intracranial hemangioblastoma. Radioimmunoassay showed an elevated level of erythropoietin in her serum. Cyst fluid from the tumor also contained erythropoietin, concentrated a thousandfold relative to the serum level. Production of erythropoietin by hemangioblastomas may explain the erythrocytosis present in some patients with von Hippel-Lindau disease.

Brain Neoplasms↗

Intracranial arachnoid cysts in children. A comparison of the effects of fenestration and shunting.

The best operative intervention for children with arachnoid cysts remains the subject of controversy. Recent reports stress that craniotomy for cyst fenestration is associated with a low incidence of morbidity and mortality and may leave the child shunt-independent. The cases of 40 pediatric patients with arachnoid cysts treated between 1978 and 1989 are reported. Five children with mild symptoms and small cysts that remained stable on follow-up studies have not required surgical intervention. Of 15 patients with cysts initially treated by fenestration, 10 (67%) showed no clinical or radiographic improvement postoperatively and have undergone cyst-peritoneal (eight patients) or ventriculoperitoneal (VP) shunting (one patient), or revision of a VP shunt placed for hydrocephalus before cyst fenestration (one patient). Two other patients with existing VP shunts required no further procedures. Thus, only three (20%) of 15 patients initially treated by fenestration remain shunt-independent after a median follow-up period of 8 years. The 20 other patients were initially treated by cysts shunting and all improved postoperatively; shunt revision has been necessary in six (30%) of these 20 patients because of cysts recurrence. Cyst location influenced the success of shunt treatment; none of the seven middle cranial fossa cysts treated by shunting have required revision, but results with cysts in other locations were less favorable. In all locations, though, shunting was more successful than fenestration. It is concluded that cyst-peritoneal or cyst-VP shunting is the procedure of choice for arachnoid cysts in most locations, including those in the middle cranial fossa.

Arachnoid↗

Magnetic resonance imaging of vertebrobasilar ectasia in tic convulsif. Case report.

A patient with trigeminal neuralgia and hemifacial spasm was evaluated using multiplanar magnetic resonance (MR) imaging with gadolinium enhancement. Preoperative images demonstrated massively ectatic vertebral and basilar arteries and their distortion of the brain stem and the trigeminal and facial nerves. Surgical manipulation included selective trigeminal rhizotomy, cushioning of the residual nerve at the point of maximal distortion by the underlying basilar artery, and microvascular decompression of the seventh nerve from the anterior inferior cerebellar artery which was being pushed dorsomedially by the vertebral artery. Postoperatively, the patient had neither trigeminal neuralgia nor facial spasm. Gadolinium-enhanced MR imaging not only excludes other etiologies such as tumor or arteriovenous malformation, but also demonstrates cranial nerve compression by ectatic vertebral and basilar arteries. The choice of preoperative imaging modality is discussed and the literature concerning the etiology of tic convulsif is reviewed.

Basilar Artery↗

Platelet derived growth factor (PDGF) autocrine components in human tumor cell lines.

Tumor cells may stimulate their own proliferation through an autocrine mechanism by simultaneously producing growth factors and growth factor receptors. We now report that numerous human tumor-derived cell lines simultaneously express the genes for platelet-derived growth factor (PDGF) A and B chains and the PDGF receptor (PDGF-R). Measurement of mRNA transcribed from these genes showed that among 16 malignant glioma cell lines tested, 15 expressed the PDGF A gene, 12 expressed the PDGF B gene, and 13 expressed the PDGF-R gene. Of three osteosarcoma lines, three expressed PDGF A, two expressed PDGF B, and three expressed PDGF-R. For eight malignant melanoma lines, seven expressed PDGF A, five expressed PDGF B, and three expressed PDGF-R genes. Thus, 13 of 16 malignant glioma, 3 of 3 osteosarcomas, and 3 of 8 malignant melanoma cell lines expressed the PDGF receptor gene and either or both PDGF genes. Five cell lines were tested for production of biologically active PDGF and PDGF receptor protein. Media conditioned by each of the five cell lines induced tyrosine phosphorylation of a protein identical in size to the PDGF receptor. These five cell lines also produced PDGF receptor protein as measured by Western blot analysis or metabolic labeling and immunoprecipitation using PDGF-R antibodies. The PDGF receptors of these cell lines were activated by human platelet PDGF or by recombinant AA or BB homodimers. Intracellular interaction of these receptors with the growth factor simultaneously produced may provide continuous stimulation to the proliferation of these cells.

Animals↗

Radiation-induced bilateral cystic temporal lobe necrosis: reversal of memory deficit after fenestration and internal shunting. Case report.

The authors report a case in which bilateral cystic temporal lobe necrosis developed after treatment of nasopharyngeal lymphoepithelioma with 7000 cGy of external beam radiation. The patient presented with an isolated memory deficit that was documented by neuropsychological testing. After fenestration and internal shunting of both cysts, there was striking resolution of the lesions and of the memory deficit.

Brain Diseases↗

Oncogene-related growth factors and growth factor receptors in human malignant glioma-derived cell lines.

Oncogenes induce malignant transformation of cells. Two oncogenes are closely related to genes coding for a mitogenic growth factor (v-sis to the PDGF gene) and a receptor for a mitogenic growth factor (v-erb B to the EGF receptor gene). We studied the possibility that cells derived from malignant gliomas produce mitogenic factors that bind to cell surface receptors, the activation of which could lead to excessive stimulation of cell proliferation. All six cell lines tested secrete into their medium factors that stimulate DNA synthesis. The factor secreted by one cell line was characterized and found to resemble PDGF. Six of 11 cell lines had receptors for PDGF demonstrable by binding and receptor autophosphorylation assays. Six of six cell lines tested had EGF receptors demonstrable by binding and receptor autophosphorylation experiments. The extremely high levels of EGF receptor in one cell line may reflect excessive expression of the erb B oncogene associated with abnormalities of chromosome 7 that occur in this cell line.

Cell Division↗

Cyclic AMP blocks expression of the c-sis gene in tumor cells.

Some human tumor cell lines express the c-sis gene, the proto-oncogene of the transforming gene v-sis, and produce platelet-derived growth factor, which may contribute to carcinogenesis by autocrine or paracrine mechanisms. Here we demonstrate that c-sis expression in some human glioma and osteosarcoma cell lines can be blocked by agents that increase cellular cyclic adenosine monophosphate (cAMP). Forskolin, 8-bromocyclic AMP, cholera toxin, and prostaglandin E1 reduced c-sis mRNA in these cells by up to 90%. c-sis transcription rates were reduced by agents that increase cAMP; the stability of c-sis mRNA was unaffected. The possible therapeutic value of blocking the expression of tumor growth factor genes pharmacologically warrants further study.

Colforsin↗