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Biomedical subjects

W F Chandler

Publications and source records attributed to W F Chandler.

At least 73 records · Page 4Linked to original sources

The spectrum of ACTH-producing pituitary lesions.

The immunohistochemical characterization of 92 surgically resected abnormal pituitaries showed 24 cases with ACTH immunoreactivity. These included two cases of nodular hyperplasias, 20 functional adenomas, and two silent corticotropic adenomas. Both patients with nodular hyperplasia and 19 patients with functional adenomas had Cushing's disease, while one patient with a functional adenoma had Nelson's syndrome. The two silent corticotropic adenomas were not associated with Cushing's disease, although both patients had slightly elevated serum prolactin levels. The tumors, which were stained for beta-endorphin (12 cases) and alpha and beta-MSH (five cases) were all positive for these peptides. These results show that immunohistochemical staining is indispensable in the diagnosis of nodular hyperplasia and silent corticotropic adenomas and that it is extremely helpful in confirming the diagnosis of ACTH-producing adenomas.

Adenoma↗

Cushing's syndrome secondary to ectopic corticotropin-releasing hormone-adrenocorticotropin secretion.

A 47-yr-old woman with severe Cushing's syndrome had a bronchial carcinoid secreting ACTH and corticotropin-releasing hormone (CRH) and associated pituitary corticotroph hyperplasia. While the clinical picture was consistent with the ectopic ACTH syndrome, the biochemical pattern was that of pituitary ACTH-dependent hypercortisolism. Both plasma ACTH and CRH levels were high. However, while plasma ACTH increased during metyrapone administration and decreased during administration of high dose of dexamethasone, plasma CRH levels did not change, suggesting a direct pituitary response to these testing maneuvers. Immunoperoxidase staining of the tumor tissue confirmed the presence of ACTH and CRH, and the finding of an ACTH and a CRH concentration gradient across the tumor bed indicated that the tumor was actively secreting these two hormones. Cytochemical heterogeneity was seen in the tumor, in which two distinct populations of cells, one secreting ACTH and beta-endorphin and the other secreting CRH, were identified. This patient, thus, had an unusual syndrome of ectopic ACTH and ectopic CRH secretion.

ACTH Syndrome, Ectopic↗

Intracranial extension of orbital pseudotumor: a case report.

A patient with intracranial extension of an orbital pseudotumor is reported. This rare consequence of an unusual inflammatory process has been reported on only two previous occasions. Our patient initially presented with unilateral loss of vision and a mass in the sphenoid sinus. Transsphenoidal biopsy revealed inflammatory tissue with a predominance of plasma cells. Over 2 years later, computed tomographic scanning demonstrated involvement of the ipsilateral frontal lobe, and craniotomy revealed invasion of both the dura mater and the cortex by this inflammatory process. Immunohistochemical staining for B and T cells was done to rule out lymphoma, and extensive cultures and staining were performed to identify any infectious process. Because this progressive lesion did not respond to steroid treatment, radiation therapy to the affected area was carried out. Orbital pseudotumor should be considered when an inflammatory process is identified in the meninges and cortex of the anterior fossa.

Female↗

The spectrum of pituitary adenoma hemorrhage.

In 34 cases of pituitary adenoma hemorrhage at one institution, the clinical manifestations of adenoma hemorrhage depended upon the size of the adenoma, the presence of suprasellar extension, the amount of hemorrhage and the extent of pituitary glandular destruction. Recognition of the spectrum of acute, subacute and chronic pituitary adenoma hemorrhage should expedite diagnosis and treatment.

Adenoma↗

Symptomatic Rathke's cleft cyst with pituitary adenoma: case report.

A rare case of a pituitary adenoma found in association with a symptomatic Rathke's cleft cyst in a 34-year-old women presenting with headaches, visual symptoms, and amenorrhea is described. The diagnostic evaluation and operative treatment of these coincident lesions are discussed.

Adenoma↗

Stromal and nuclear markers for rapid identification of pituitary adenomas at biopsy.

We tested fluorescent and light microscopic markers to improve recognition of pituitary adenomas at biopsy. The optimal reagent was 100 mg/L of fluoresceinated Ricinus communis agglutinin 120 (RCA 120) lectin plus 3 mg/L of propidium iodide. The refrigerated solution was immediately available for use on routine frozen sections. The sections were stained for one minute and viewed immediately after they were rinsed with saline and coverslips applied. Fluorescein-labeled RCA 120, which binds galactose, localized vascular stroma. Propidium iodide, which binds nucleic acids, stained nuclei. Stromal configuration, nuclear morphology, and cell to stroma ratio were illuminated and used to distinguish adenoma from adenohypophysis. We also describe a method utilizing peroxidase-conjugated RCA 120 that demonstrates the same features by light microscopy. Fluoresceinated RCA 120-stained vessels and stroma of routinely processed material more reliably than hematoxylin-eosin or labeled antibody to fibronectin and faster than peroxidase-conjugated RCA 120 or the rapid method for reticulin.

Adenoma↗

Real-time sonography during spinal surgery.

Real-time sonography was performed during spinal surgery in eight adult patients with seven different types of lesions. Cervical, thoracic, and lumbar lesions were included. All were examined prior to dural opening, using the saline-filled wound for water-path imaging. Five extramedullary masses and two intramedullary cavities were well delineated, allowing optimal surgical access to be determined at the moment of approach. Sonography also was abnormal in one case of diffuse spinal cord expansion, but no tissue sonographically distinguishable from spinal cord substance could be identified. Adequacy of surgical treatment was evaluated by repeat sonography before dural closure in one case of extramedullary mass and two cases of intramedullary cavities. Sonography is both reliable and beneficial during surgery for a variety of intraspinal lesions.

Adult↗

Intraoperative sonographic delineation of low-grade brain neoplasms defined poorly by computed tomography.

Sixty-four consecutive primary or metastatic brain tumors were reviewed to assess the efficacy of intraoperative sonography for localization, biopsy, and/or drainage. In 12 cases, preoperative CT data were incomplete or confusing, usually due to low-density, non-enhanced areas in which low-grade tumor could not be reliably differentiated from necrosis, edema, or cyst. In each case, intraoperative sonography clarified the nature of the solid tumor component by its distinct hyperechogenicity, facilitating biopsy. As a guide to surgical biopsy of brain tumors, sonography has some advantages even over stereotactic systems, which depend upon accurate CT definition of the lesion.

Adult↗

Real time ultrasound characteristics of the acute intracerebral hemorrhage as studied in the canine model.

Real time intraoperative sonography is a valuable tool for visualizing subcortical mass lesions. Although most solid lesions are hyperechogenic, little is known about the ultrasound characteristics of intracerebral hemorrhage and subsequent hematoma formation. We sought to determine the sonographic characteristics of an acute intracerebral hematoma, to study its evolution, and to explore factors responsible for its echogenicity. Acute intracerebral hematomas were created in adult mongrel dogs using heparinized or unheparinized autologous whole blood injected under sonographic visualization into the centrum semiovale of 10 cerebral hemispheres. Different components of blood were also imaged in polyurethane test tubes (n = 56) immersed in a degassed, room temperature water bath. All studies were performed with continuous ultrasound recording using the ATL real time Neurosector scanner with the variable 3-, 5-, and 7.5-MHz transducer. Intracerebral hematomas were initially hypoechogenic, becoming hyperechogenic between 16 and 23 seconds after injection (average, 22 seconds). Full echogenicity was obtained between 40 and 213 seconds after injection (average, 91 seconds). There was no difference between the sonographic appearances of hematomas formed with whole blood and those formed with heparinized whole blood. In addition, we demonstrated the superior sensitivity of the 7.5-MHz frequency in visualizing intracerebral hematomas in vivo, as opposed to the 3- and 5-MHz frequencies. Whole blood, heparinized whole blood, and citrated whole blood were found to be highly echogenic in vitro. Phosphate-buffered saline, plasma, serum, and packed red blood cells (PRBCs) were hypoechogenic. Resuspended PRCBs in phosphate-buffered saline, plasma, or serum were echogenic. Our data suggest that hyperechogenicity is independent of the clotting mechanism and is related to blood stasis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of different aspirin doses on arterial thrombosis after canine carotid endarterectomy: a scanning electron microscope and indium-111-labeled platelet study.

Although it is widely accepted that aspirin inhibits platelet aggregation in arterial thrombosis, the appropriate dosage of aspirin remains quite controversial. The purpose of this study was to determine the effect of different doses of aspirin (0.5 mg/kg vs. 10 mg/kg) on mural thrombus formation after carotid endarterectomy. Eighteen hours after oral aspirin administration, 20 endarterectomies were performed on mongrel dogs with the use of the operating microscope. Blood flow was then restored for 3 hours and the vessels were prepared for investigation with the scanning electron microscope. Ten endarterectomies were also performed on unmedicated dogs as controls. Five minutes before vessel unclamping, autologous indium-111-labeled platelets were administered intravenously, and the endarterectomized portions of the vessels were studied with a gamma counter system after harvesting. Group 1, the control group, revealed extensive mural thrombus consisting of platelet aggregates, fibrin, red blood cells, and white blood cells. Six of the 10 vessels in Group 2, premedicated with 0.5 mg of aspirin per kg, demonstrated varying amounts of mural thrombus. Group 3 (10 vessels), premedicated with 10 mg of aspirin per kg, revealed a platelet monolayer completely covering the exposed vessel wall media, with scattered white blood cells and infrequent fine fibrin strands overlying the platelet surface. The mean (+/- SD) radioactivity per group expressed as counts/minute/mm2 was: Group 1--2055.3 +/- 1905.5, log = 7.253 +/- 0.926; Group 2--1235.6 +/- 1234.3, log = 6.785 +/- 0.817; Group 3--526 +/- 433.06, log = 5.989 +/- 0.774.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Intra-arterial BCNU chemotherapy for treatment of malignant gliomas of the central nervous system.

Because of the rapid systemic clearance of BCNU (1,3-bis-(2-chloroethyl)-1-nitrosourea), intra-arterial administration should provide a substantial advantage over intravenous administration for the treatment of malignant gliomas. Thirty-six patients were treated with BCNU every 6 to 8 weeks, either by transfemoral catheterization of the internal carotid or vertebral artery or through a fully implantable intracarotid drug delivery system, beginning with a dose of 200 mg/sq m body surface area. Twelve patients with Grade III or IV astrocytomas were treated after partial resection of the tumor without prior radiation therapy. After two to seven cycles of chemotherapy, nine patients showed a decrease in tumor size and surrounding edema on contrast-enhanced computerized tomography scans. In the nine responders, median duration of chemotherapy response from the time of operation was 25 weeks (range 12 to more than 91 weeks). The median duration of survival in the 12 patients was 54 weeks (range 21 to more than 156 weeks), with an 18-month survival rate of 42%. Twenty-four patients with recurrent Grade I to IV astrocytomas, whose resection and irradiation therapy had failed, received two to eight courses of intra-arterial BCNU therapy. Seventeen of these had a response or were stable for a median of 20 weeks (range 6 to more than 66 weeks). The catheterization procedure is safe, with no immediate complication in 111 infusions of BCNU. A delayed complication in nine patients has been unilateral loss of vision secondary to a retinal vasculitis. The frequency of visual loss decreased after the concentration of the ethanol diluent was lowered.

Adult↗

Abnormal serum melatonin levels in patients with intrasellar tumors.

Melatonin, a pineal indoleamine, is postulated to be of importance in a regulatory fashion in hypothalamic and pituitary function. Attempts to utilize its random serum level as a consistent marker of pineal tumors have not been successful. Fifteen patients were studied to determine whether the normal diurnal variation in serum melatonin as determined by radioimmunoassay was altered by the presence of an intrasellar pituitary region tumor. A normal diurnal cycling of melatonin (high level at night, low level at midday coupled to the light-dark cycle) was seen in controls consisting of patients admitted for spinal or supratentorial procedures (a.m. melatonin, 15.4 +/- 3.7 pg/ml; p.m. melatonin, 57.1 +/- 16.3 pg/ml). This normal pattern of melatonin levels was altered in the group of patients with intrasellar tumors (a.m. melatonin, 28.9 +/- 6.7 pg/ml; p.m. melatonin, 28.4 +/- 7.3 pg/ml). Hospitalization and operation caused nonspecific alterations in the pattern of melatonin in both groups. These results suggest that the pattern of secretion rather than the absolute midday value of melatonin may be of greater importance as evidence of altered pineal and pituitary neuroendocrine regulation.

Adenoma↗

Prolactin and growth hormone-producing pituitary adenomas. An immunohistochemical and ultrastructural study.

Thirteen prolactin and five growth hormone-producing pituitary adenomas were studied by immunohistochemistry and electron microscopy. The immunohistochemical localization of prolactin and growth hormone correlated well with elevated serum levels of pituitary hormones in all cases. Ultrastructural characterization by granule density and secretory activity was studied in relation to the serum levels of pituitary hormones and the sizes of the tumors. This indicated that markedly elevated serum hormone levels were related to larger tumors with high secretory activity, as indicated by abundant endoplasmic reticulum and well-developed Golgi complexes rather than to the numbers of cytoplasmic granules in the tumors. Two patients with prolactin-producing adenomas had been treated with bromocryptine before surgery. Both tumors showed evidence of degeneration, including cytoplasmic vacuolization. In one case the tumor had an increased number of secretory granules, while in the other case there were few viable cells and an abundance of amyloid deposits. The effects of bromocryptine therapy on pituitary tumor morphology in these two cases include an increased number of pituitary granules, and cellular degenerative changes.

Adenoma↗