Search PubMed⌕ Search

Biomedical subjects

E R Laws

Publications and source records attributed to E R Laws.

At least 109 records · Page 6Linked to original sources

Estrogen receptor gene expression in craniopharyngiomas: an in situ hybridization study.

Craniopharyngiomas are histologically benign epithelial neoplasms of the sellar region that frequently exhibit invasive and aggressive local growth. In this study, we have investigated the presence and cellular distribution of estrogen receptor messenger ribonucleic acid by in situ hybridization in 23 surgically removed craniopharyngiomas. All craniopharyngiomas studied, including 19 adamantinomatous and 4 papillary variants, uniformly expressed the estrogen receptor gene. In all cases, an intense estrogen receptor messenger ribonucleic acid hybridization signal was demonstrated; one localized exclusively to the epithelial cells of the tumor. Connective tissue and vascular elements were devoid of hybridization signal. Coexpression of the estrogen receptor protein was also studied by immunohistochemistry. Despite the relative abundance of estrogen receptor message in all cases studied, the estrogen receptor protein was focally but conclusively detected in only two tumors. The basis of this discrepancy is unclear. Progesterone receptor protein was also studied in all cases; however, its definitive presence was noted in only one instance and, in that case, in only occasional nuclei. The expression of the estrogen receptor gene by the proliferative epithelial elements of craniopharyngiomas raises the questions of a possible hormonal component to the genesis and/or progression of the craniopharyngiomas and a potential responsiveness to therapeutic hormonal manipulation.

Cell Division↗

Pituitary adenomas in childhood and adolescence. Results of transsphenoidal surgery.

Pituitary adenomas are uncommon in childhood. Between 1975 and 1988, 36 patients underwent transsphenoidal resection at the Mayo Clinic before their 17th birthday. Fifteen (41.7%) had prolactin (PRL)-secreting tumors, 16 (44.4%) had adrenocorticotropic hormone (ACTH)-secreting tumors (including two patients with Nelson-Salassa syndrome), and three (8.3%) had tumors secreting growth hormone (GH); two patients (5.6%) had clinically nonfunctioning tumors. Of the 36 patients, 21 (58.3%) were girls, and girls predominated in every group except that with ACTH-secreting tumors, where they accounted for only 37.5% of the patients. The average age at the time of surgery was 14.7 +/- 2.2 years, the youngest patient being 7.3 years old. The ACTH-secreting tumors were associated with an earlier onset of symptoms than the other tumor types: six (37.5%) of 16 patients became symptomatic before 10 years of age, compared with two (10.0%) of the 20 other patients. Presenting symptoms primarily reflected endocrine dysfunction, with neurological presentation (visual field deficits) occurring in only two patients. There were no deaths in this patient group. Significant operative morbidity included steroid-induced psychosis in one patient and diabetes insipidus in three, which resolved in two. Plurihormonal tumors, broadly defined as tumors producing more than one hormone, were common, comprising five (36%) of 14 PRL-secreting tumors, all three GH-secreting tumors, and one of two clinically nonfunctioning tumors, or 25.7% overall. Macroadenomas accounted for 89% of plurihormonal tumors. Long-term follow-up review (median > 5 years) revealed good control of PRL-secreting tumors (although five of 15 patients had received postoperative radiotherapy), contrasted with a 25% late recurrence rate for ACTH-secreting tumors, which had an 80% initial remission rate. The majority of patients had good endocrine function, including reproductive function. It is concluded that: 1) although pediatric pituitary adenomas occur primarily in adolescence, Cushing's disease is found at any age; 2) transsphenoidal surgery is feasible and safe in this age group; 3) plurihormonal tumors occur more frequently in the pediatric age group than in adults; and 4) long-term control rates in PRL- and ACTH-secreting tumors are probably similar to those seen in adults.

Adenoma↗

The binding influence of the Journal of Neurosurgery on the evolution of neurosurgery.

The author, who is currently a member of the Editorial Board of the Journal of Neurosurgery, examines the development of the specialty of neurosurgery and the timing of first publication of the Journal. He describes the role played by the Journal in the constantly advancing specialty and its importance to neurosurgery as a whole.

History, 20th Century↗

Lymphocytic hypophysitis: occurrence in two men.

Two men undergoing transsphenoidal exploration for pituitary adenoma were found to have lymphocytic hypophysitis. Both presented with frontal headaches, lethargy, and diminished libido. Laboratory investigations showed markedly depressed serum testosterone, and magnetic resonance imaging demonstrated pituitary enlargement, with optic chiasm involvement. Intraoperatively, the dura was adherent to the pituitary in each case. The resected glands were effaced by a dense lymphoplasmacytic infiltrate and fibrosis, without granulomas. Nonspecific peripheral enhancement on imaging suggested a diagnosis other than adenoma, but more experience with peripheral enhancement in lymphocytic hypophysitis is needed. The diagnosis was histological and required surgical intervention. Long-term pituitary replacement therapy is usually required.

Adenoma↗

Chordoma of the mobile spine. A clinicopathologic analysis of 40 patients.

BACKGROUND: Chordomas are lobulated neoplasms composed of physaliphorous cells and their precursors; some have atypical, epithelioid, or spindle cell features. Fewer than one-sixth of chordomas arise in the mobile (cervical, thoracic, or lumbar) spine. Forty-eight percent originate in the sacrococcygeal region and 39% in the sphenoocciput. METHODS: The study included 40 patients, 27 men and 13 women (2:1), with chordoma of the mobile spine. Their clinical and histopathologic features are described. RESULTS: Nineteen tumors (48%) were located in the cervical spine, 7 (17%) in the thoracic spine, and 14 (35%) in the lumbar area. Most patients underwent subtotal removal of the tumor and postoperative irradiation. Variations in histologic appearance, including an occasional chondroid background, did not affect biologic behavior. Twenty-three patients (58%) were alive 5 years after surgery. Eventually, 25 patients (63%) died of tumor. Metastasis developed in two patients (5%). In contrast to some other studies metastasis was a rare occurrence. CONCLUSION: Chordoma of the mobile spine is a slow-growing, recurring neoplasm of low metastatic potential that incapacitates by locally aggressive growth.

Adult↗

Migration of human malignant astrocytoma cells in the mammalian brain: Scherer revisited.

Fresh suspensions of human glioblastoma multiforme were preincubated in the plant lectin Phaseolus vulgaris leucoagglutinin (PHAL) and implanted into cortical pockets in adult rat brain. Brains were investigated periodically over 30 postoperative days and the migration of the human glioblastoma cells was traced with anti-PHAL immunofluorescence or the overexpression of human specific p185c-neu a specific marker of a class of human malignant astrocytoma cells. The principal pathway of migration of the implanted human cells in the rat brain was ventrally through cortical gray matter and into the corpus callosum, with rapid lateral distribution in this and other parallel and intersecting white matter fascicles. Human glioblastoma cells also migrated on basement membrane lined blood vessels, pia-glia membrane and spaces of Virchow-Robin, as well as the subependymal space of the ventricles. These paths of migration of human glioblastoma cells in the rat brain are consistent with the pathways of spread of glioblastoma in the human brain as described by Scherer over 50 years ago, indicating that multifocal malignant astrocytomas have common migratory pathways in mature mammalian brain.

Animals↗

Pit-1 messenger ribonucleic acid is differentially expressed in human pituitary adenomas.

Thirty-four human pituitary adenomas were examined for the presence of Pit-1 mRNA via Northern analysis. All tumors that were immunoreactive with either human (h) PRL or hGH antiserum contained Pit-1 mRNA (8 of 8) as did a small percentage of alpha-subunit only (1 of 3) and null tumors (1 of 9). Two tumors that contained TSH beta mRNA by RNAse protection assay also contained Pit-1 mRNA. Tumors that were immunoreactive with antiserum for hACTH, hFSH beta, or hLH beta without containing PRL, GH, or TSH beta were uniformly Pit-1 negative (0 of 14). Although RNA from the majority of Pit-1-positive tumors (10 of 11) contained primarily a 2.4-kilobase (kb) Pit-1 mRNA transcript, 1 tumor appeared to contain a 1.6-kb mRNA. Analysis of human pituitary autopsy specimens revealed no 1.6-kb Pit-1 mRNA, indicating that this variant may be tumor specific. The wide variety of serum PRL, GH, and insulin-like growth factor-I levels in patients with Pit-1-positive tumors suggests that although Pit-1 is necessary for PRL and GH production, it is not uniformly associated with hormone production, as determined by either immunohistochemistry or elevated serum levels. The expression of Pit-1 mRNA in a small fraction of null and alpha-subunit only tumors indicates that there may be a previously unsuspected diversity of origin within these particular subsets of adenomas.

Adenoma↗

A retrospective analysis of pituitary apoplexy.

Thirty-seven patients with pituitary apoplexy were analyzed with an emphasis on clinical presentation and visual outcome. Their mean age was 56.6 years, with a male to female ratio of 2:1. Presenting symptoms included headache (95%), vomiting (69%), ocular paresis (78%), and reduction in visual fields (64%) or acuities (52%). Computed tomographic scanning correctly identified pituitary hemorrhage in only 46% of those scanned. Thirty-six patients underwent transsphenoidal decompression. By immunostaining criteria, null-cell adenomas were the most frequent tumor type (50%). Long-term steroid or thyroid hormone replacement therapy was necessary in 82% and 89% of patients, respectively. Long-term desmopressin therapy was required in 11%, and 64% of the male patients required testosterone replacement therapy. Surgery resulted in improvement in visual acuity deficits in 88%, visual field deficits in 95%, and ocular paresis in 100%. Analysis of the degree of improvement in preoperative visual deficits with the timing of the surgery demonstrated that those who underwent surgery within a week of apoplexy had significant recovery in their visual acuities. In the stable, conscious patient with residual vision in each eye, surgical decompression should be performed as soon as possible, because delays beyond 1 week may retard the return of visual function.

Adenoma↗

Human-specific c-neu proto-oncogene protein overexpression in human malignant astrocytomas before and after xenografting.

Overexpression of human-specific c-neu proto-oncogene transmembrane tyrosine kinase receptor protein (p185) is an index of cell transformation and of poor patient survival in several malignancies. The authors studied this protein in low- and high-grade human malignant astrocytomas before and after xenografting into aspiration pockets in rat cortex. Human-specific p185c-neu-positive cells were found in tumor specimens from all grades of astrocytoma. Significantly fewer p185c-neu-positive cells were observed in the low-grade versus the high-grade astrocytomas examined (p < 0.05). Human specific p185c-neu-positive cells were also positive for the human major histocompatibility complex, human leukocyte antigen (HLA)-DR, as well as glial fibrillary acidic protein and S-100 protein. Fresh suspensions of tumor tissue were prelabeled with the plant lectin Phaseolus vulgaris leukoagglutinin and xenografted into pockets in rat cortex. A class of human p185c-neu-positive cells found in tissue samples from all grades of astrocytoma migrated in the rat brain along parallel and intersecting nerve fibre bundles and basement membrane-lined surfaces. Migrated p185c-neu-positive cells were also positive for HLA-DR, Phaseolus vulgaris leukoagglutinin, glial fibrillary acidic protein, and S-100 protein, suggesting that they were in fact human astrocytoma cells. Simultaneous expression of human p185c-neu, HLA-DR, and glial fibrillary acidic protein was observed in a class of human malignant astrocytoma cells in both tumor tissue and xenografted cells that migrated into rat brain. These molecules are signature proteins for the study of the spread of human malignant astrocytomas in an animal model, and indicate that transformed human malignant astrocytoma cells can migrate within the parenchyma of the central nervous system and could play a role in the development of multifocal tumors.

Animals↗

Results of surgical treatment for growth hormone-secreting pituitary adenomas.

The results of surgical therapy for acromegaly were reviewed in a series of 175 patients treated between 1972 and 1983. Patients with prior surgery or radiation therapy were excluded from the study. Postoperative radiation therapy was given to 54 patients. The criterion of achieving a postoperative basal or glucose-suppressed growth hormone level of 2 ng/ml or less was used to indicate remission. Utilizing the most recently available growth hormone determinations, 90 (51.7%) of 174 patients were in remission. The actuarial probability of remission at 1 and 5 years after surgery was 48.8% and 62.7%, respectively. Tumor size and the preoperative basal growth hormone level were correlated with outcome. Surgical excision of a pituitary adenoma is the most effective therapy currently available for acromegaly.

Adenoma↗

Mechanisms of C6 glioma cell and fetal astrocyte migration into hydrated collagen I gels.

Fetal basal ganglia astrocytes and C6 glioma cells were plated on the surface of 1.5 cm thick hydrated collagen I wafers. Both cell types migrated through the entire thickness of the wafer within 1 day after plating. The collagen in the wafer was digested and the fine collagen I fibrils were clumped into large strands. By 2-3 days, the collagen strands were digested from the wafers and replaced by a mass of fetal astrocytes or C6 cells joined by their processes. The collagen I digestion and cell migration suggested protease production. In a second series of experiments, cultured C6 cells and E14 fetal astrocytes were immunohistochemically stained for the presence of plasminogen activators as an index of protease production. Both tissue (tPA) and urokinase (uPA) types were observed. Fetal astrocytes and C6 cells were also positive for guanidinobenzoatase, a serine protease associated with migrating cells. These data demonstrate that rapid migration of the cells on and through collagen I fibrils is concomitant with expression of plasminogen activators and proteases which can either activate or function as collagenases and release the cells from the substrate.

Animals↗

Case report: acromegaly and Cushing's disease in a patient with synchronous pituitary adenomas.

A 40-year-old white woman presented with hirsutism, amenorrhea, generalized fatigue, diffuse weight gain, acral changes, and coarsened facial features. Physical examination revealed mild diastolic hypertension, acromegalic features, hirsutism, and seborrhea. The growth hormone concentration was elevated and did not suppress after glucose administration. Urinary free cortisol excretion was increased and was not suppressed during a 2 mg low-dose dexamethasone suppression test. Magnetic resonance imaging of the sella demonstrated a 1.3 x 1.2 x 0.8 cm pituitary adenoma. Trans-sphenoidal resection was performed, and portions of the resected tumor were analyzed by routine pathologic methods. Histopathologic and immunohistochemical findings indicated discrete growth hormone- and adrenocorticotropic hormone-producing pituitary adenomas. Coexisting acromegaly and Cushing's syndrome due to pituitary neoplasia was previously reported in two patients. However, to the authors' knowledge, this represents the first description of a patient with acromegaly and Cushing's disease resulting from discrete synchronous adenomas of the pituitary gland as defined by modern histopathologic techniques.

17-Ketosteroids↗

Resection for solitary brain metastasis. Role of adjuvant radiation and prognostic variables in 229 patients.

The authors reviewed 229 consecutive patients treated intramurally by resection of solitary cerebral metastasis. Patients were classified into four groups on the basis of whether a gross total resection or subtotal resection was performed and whether systemic disease was present or absent at the time of craniotomy. Group 1 had gross total resection and no systemic disease; Group 2 had subtotal resection and no systemic disease; Group 3 had subtotal resection and systemic disease; and Group 4 had gross total resection and systemic disease. All four groups were further subdivided into Subgroup A (adjuvant whole-brain radiation therapy) or Subgroup B (no adjuvant radiation). Data were collected regarding multiple patient and tumor variables for multivariate analysis. Survival data for the 46 patients in Group 1A (median 1.3 years, 2-year survival rate 41%, 5-year survival rate 21%) were markedly better than those for the 75 in Group 1B (median 0.7 year, 2-year survival rate 19%, 5-year survival rate 4%). The 20 patients in Group 2A also had superior survival data (median 1.1 years, 2-year survival rate 30%, 3-year survival rate 30%) when compared with the eight patients in Group 2B (median 3 months, 1-year survival rate 0%). However, the 16 and 22 patients in Groups 3A and 4A, respectively, had no discernible differences compared to the seven and 35 patients in their Group 3B and 4B counterparts. Multivariate analyses were performed to assess the association of survival with multiple patient, disease, and treatment variables. Poor neurological status and systemic disease were significantly associated with inferior survival, while longer (greater than 36 months) intervals between primary diagnosis and craniotomy were significantly associated with improved survival. After adjusting for the effects of other patient, disease, and treatment characteristics, adjuvant whole-brain radiotherapy was significantly associated with improved survival times. These data support the continued use of craniotomy followed by adjuvant whole-brain radiation therapy for treatment of solitary brain metastasis. However, this aggressive therapy appears relatively contraindicated in the face of either systemic disease or substantial neurological deficit.

Adolescent↗