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Biomedical subjects

W F Chandler

Publications and source records attributed to W F Chandler.

At least 55 records · Page 3Linked to original sources
PubMed1988

Intra-arterial 5-bromo-2-deoxyuridine (BUdR) radiosensitization with external beam radiation in rhesus monkeys: toxicity study.

A primate toxicity study was performed to test the hypothesis that BUdR does not increase the likelihood of unilateral or bilateral central nervous system damage secondary to radiation therapy. BUdR, a halogenated pyrimidine analog is incorporated into DNA of dividing cells and sensitizes them to radiation. It is best given unilaterally, intra-arterially by continuous infusion because of its regional advantage (Rd) estimated to be between 11 and 16. Six rhesus monkeys were implanted with a Model 400 Infusaid pump perfusing the right internal carotid artery. Three of the six monkeys received intra-arterial (IA) BUdR infusion plus whole brain external beam radiation (6,000 R over 6 weeks) and three received radiation alone. The two BUdR treated animals completing radiation developed symmetric bilateral high signal aberrations on MRI in the frontal, parietal, and occipital centrum semiovale and corona radiata at nine months. At autopsy, confluent microinfarcts were found to correspond topographically to the MRI abnormalities. In the radiation alone group, two animals had normal MRI and autopsy while the third animal had bilateral MRI high signal aberrations develop sequentially with corresponding microinfarcts at autopsy. These changes were greater in severity than those seen in the BUdR treated animals. We support previous evidence that there is differential intraspecies sensitivity to radiation. We find that BUdR produces no unilateral potentiation of radiation toxicity.

Animals↗
PubMed1988

Analysis of mammosomatotropic cells in normal and neoplastic human pituitary tissues by the reverse hemolytic plaque assay and immunocytochemistry.

The reverse hemolytic plaque assay (RHPA) was used to study hormone release from cultured normal and neoplastic human pituitary cells. The RHPA revealed a lower percentage of GH- and PRL-producing cells in normal and neoplastic pituitaries compared to the percentage of these cells revealed by immunocytochemical (ICC) staining for GH and PRL. Normal pituitary tissues as well as some PRL- or GH-producing adenomas contained large numbers of mammosomatotropic (MS) cells when analyzed by RHPA, combined RHPA-ICC, and ultrastructural immunohistochemistry with immunogold labeling. The percentage of GH and PRL cells in normal pituitaries ranged from 37-51% and 30-60%, respectively, by RHPA, while the percentage of MS cells ranged from 29-49%. The percentage of GH and PRL cells in normal pituitaries estimated by ICC ranged from 53-65% and 32-55%, respectively, while the percentage of MS cells estimated with this technique ranged from 26-50%. Double labeling with the immunogold technique detected GH and PRL in the same cells and within the same granules in both normal and neoplastic pituitary cells. These results indicate that MS cells are present in normal human pituitaries as well as in some pituitary adenomas, and in some pituitaries these two hormones are stored within the same secretory granules.

Adenoma↗
PubMed1988

Preoperative treatment of acromegaly with long-acting somatostatin analog SMS 201-995: shrinkage of invasive pituitary macroadenomas and improved surgical remission rate.

Ten patients with previously untreated acromegaly and invasive pituitary macroadenomas were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz) for 3-30 weeks before transsphenoidal or subfrontal pituitary adenomectomy. Preoperatively, treatment with SMS 201-995 reduced mean 24-h plasma GH concentrations from 8.5-66.7 to below 4.6 micrograms/L in eight patients and by 60-80% in the remaining two patients. Pituitary tumor size decreased 20-54%. Morphologically, the tumors showed decreased total cell, cytoplasmic, and nuclear areas; varying degrees of perivascular fibrosis; and dense granularity. Postoperatively, plasma GH and insulin-like growth factor I concentrations fell into the normal range, and GH dynamics became normal in eight patients. In the remaining two patients mild GH hypersecretion persisted after surgery (mean fasting and random plasma GH, 6.1 and 7.9 micrograms/L), and in one of them GH secretion became normal 1 yr after pituitary irradiation. Thus, preoperative administration of SMS 201-995 consistently induced shrinkage of GH-producing pituitary tumors, and the apparent remission rate was high in the treated patients.

Acromegaly↗
PubMed1988

Intraoperative color-flow Doppler imaging of AVM's and aneurysms.

The use of intraoperative color-flow Doppler sonography to image cerebral and spinal arteriovenous malformations (AVM's) and a giant aneurysm is reported in 10 patients. The technique is a useful adjunct in localizing vascular lesions, identifying feeding or draining vessels, and confirming intraoperative surgical excision of AVM's or ligation of giant aneurysms. Imaging of lesions deeper than 4 to 5 cm is, however, limited with the equipment design now commercially available.

Adult↗
PubMed1988

Intra-arterial bromodeoxyuridine radiosensitization and radiation in treatment of malignant astrocytomas.

Bromodeoxyuridine (BUdR), a nonhypoxic radiosensitizing drug, is a halogenated pyrimidine analog that is incorporated into the deoxyribonucleic acid of dividing cells in a competitive process with thymidine; BUdR also sensitizes these cells to radiation therapy. Neurons and glial cells have a very low mitotic rate. They will not incorporate BUdR and will not be sensitized. Bromodeoxyuridine is best delivered intra-arterially because of its regional advantage, calculated to be between 6 and 16. An 8-week BUdR infusion is delivered before and during radiation therapy through a permanently implanted pump with a catheter placed retrograde into the external carotid artery. Eighteen patients with malignant glioma (15 grade IV, and three grade III) were entered into a Phase I dose-escalation protocol with BUdR dosages ranging from 400 to 600 mg/sq m/day. The maximum dose that can be tolerated appears to be 400 mg/sq m/day for 8 weeks. The 18 patients entered in this study have a median Kaplan-Meier estimated survival time (+/- standard error of the mean) of 22 +/- 5 months with 11 patients still alive. Three patients are alive at 30, 29, and 21 months after diagnosis with no evidence of tumor on computerized tomography. There have been no vascular complications. Side effects in all patients have included anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, iritis, and nail ridging. Myelosuppression requiring dose reduction occurred in one patient. One patient had a Stevens-Johnson syndrome requiring termination of BUdR. It is concluded that intra-arterial BUdR may improve survival times in patients with malignant gliomas.

Adult↗
PubMed1988

Intraoperative spinal sonography in the evaluation of intramedullary tumors.

Seventeen intraoperative spinal sonographic examinations were performed in 14 patients with intramedullary spinal cord neoplasms. Results of the ultrasound exams were correlated with preoperative imaging studies, surgical findings, and histopathologic analysis of the tumors. Intraoperative spinal sonography accurately localized the intramedullary tumors, often revealing the need for extension of the initial laminectomy. The neoplasms appeared as expansile echogenic masses, with cystic components in over half. Ultrasound was as accurate as preoperative imaging in the evaluation of solid neoplasms, and was superior to computed tomography (CT) and magnetic resonance imaging (MRI) for delineating the cystic components of neoplasms. Intraoperative sonography should be used routinely in all surgical cases of intramedullary spinal cord neoplasms.

Adolescent↗
PubMed1988

Dopamine receptors in immunohistochemically characterized null cell adenomas and normal human pituitaries.

Dopamine receptors were analyzed in plasma membranes from five null cell adenomas and five normal human pituitary tissues by [3H]spiperone binding. One prolactin (PRL)-producing, one growth hormone (GH)-producing, and an adrenocorticotropic (ACTH)-producing adenoma were also analyzed for dopamine receptors. Immunohistochemical staining showed that all null cell adenomas were positive for chromogranin A, while 20 to 30% of cells in each normal pituitary stained for this marker. The dissociation constant (Kd) and maximal binding capacity (Bmax) were 1.07 +/- 0.49 nM and 148 +/- 34 fmol/mg protein for null cell adenomas and 1.23 +/- 0.20 nM and 107 +/- 21 fmol/mg protein for normal pituitary tissues. The one PRL adenoma had a similar Kd but had a 5.6-fold higher Bmax than the mean Bmax for the null cell adenomas. These results indicate that immunohistochemically characterized null cell adenomas as well as normal pituitaries express dopamine receptors, but that the binding sites in null cell adenomas are much less those in PRL-secreting adenomas.

Adenoma↗
PubMed1988

Spinal ultrasonography. Intraoperative and pediatric applications.

Ultrasonography has had limited usefulness in the diagnosis of diseases of the spine and spinal cord in older children and adults. However, its use intraoperatively in patients of all ages, and nonoperatively in infants and young children, is finding increased application. The authors, who perform and rely on spinal sonography in both clinical situations, present an overview of technique, normal anatomy, and selected pathologic entities based on their experience and the literature.

Child, Preschool↗
PubMed1987

Brain metastasis of an invasive thymoma.

A rare case of a thymoma metastatic to brain is reported. This tumor was localized intraoperatively with the use of transdural ultrasound imaging, and gross total resection was accomplished. Radiation therapy was administered to both brain and mediastinum. The growth characteristics, classification, and treatment of thymomas are discussed.

Brain Neoplasms↗
PubMed1987

Cushing's syndrome caused by an ectopic pituitary adenoma.

A 49-year old woman with a 5-year history of Cushing's syndrome was evaluated. Biochemical measurements revealed high cortisol and adrenocorticotropic hormone (ACTH) levels consistent with the ACTH-dependent type of Cushing's syndrome. However, the source of ACTH seemed to be autonomous as she demonstrated abnormal feedback control, with lack of response to metyrapone and high coses of dexamethasone. A search for an ectopic ACTH-secreting nonpituitary neoplasm was unsuccessful. Transsphenoidal pituitary exploration revealed a normal pituitary gland, but an ectopic pituitary adenoma was found incidentally in the mucosa of the sphenoid sinus. This adenoma stained strongly positive for ACTH on immunocytochemical studies. Resection of this lesion led to remission of the Cushing's syndrome. This variant of ACTH-dependent Cushing's syndrome can mimic the ectopic ACTH-dependent type and should be looked for in patients who fail to respond to pituitary operation.

17-Hydroxycorticosteroids↗
PubMed1987

Surgical treatment of Cushing's disease.

The endocrinological, radiological, surgical, and pathological experience with 34 consecutive patients operated on for Cushing's disease is presented. Preoperative endocrine evaluation demonstrated that 19 patients had "typical" endocrine patterns for pituitary adrenocorticotropic hormone (ACTH)-dependent hypercortisolism and 11 had "atypical" testing. Pituitary pathology was found in 95% of the patients with typical preoperative endocrine testing but in only 55% of those with atypical testing. Eight of 34 preoperative computerized tomography scans demonstrated tumors, which correlated in all instances with the surgical findings. Microadenomas were removed from 25 patients, 22 of whom achieved postoperative remission of endocrine symptoms. Macroadenomas were found in three patients, only one of whom achieved remission after surgery. One patient had removal of an adenoma in the pharyngeal pituitary, and in another an ectopic lung carcinoid was excised; both of these patients were in postoperative remission. Four patients underwent transsphenoidal exploration but no definitive explanation was found for their hypercortisolism; these patients were not in remission. Immunohistochemical staining was performed on every specimen and all tumors showed excessive ACTH-secreting cells. A new rapid stain of the fibrovascular stroma is described.

Adenoma↗
PubMed1987

Recombinant human tissue-type plasminogen activator therapy in acute thromboembolic stroke.

Systemic fibrinolytic therapy for acute stroke is no longer recommended because of resulting systemic fibrinolysis and the risk of intracerebral hemorrhage. Human tissue-type plasminogen activator (TPA) is a native enzyme that converts plasminogen to plasmin with subsequent clot lysis. The affinity for plasminogen is increased several-fold when the substrate is bound to fibrin. At appropriate dosage, "clot-specific" thrombolysis may be achieved at the surface of the thrombus without creating systemic fibrinolysis. The authors designed a study to evaluate the effect of intravenous TPA administered 2 hours after acute thromboembolic stroke in rats. This time course was chosen to simulate an analogous clinical situation. Middle cerebral artery embolic stroke was caused by intracarotid injection of 0.025 cc of human blood clot in 16 rats. Regional cerebral blood flow, measured by the hydrogen clearance technique, and electroencephalographic (EEG) recordings were obtained every 30 minutes for 5 hours after thromboembolism. Eight rats received a 1-hour infusion of intravenous TPA (1.5 mg/kg) 2 hours after injection of emboli. Ipsilateral blood flow increased significantly within 30 minutes after intravenous TPA and reached preembolic levels within 60 minutes. Blood flow did not improve in the eight control rats throughout the experiment. Power spectral analysis of the EEG recordings showed improvement in the treated group compared to the control group. Postmortem angiography revealed proximal middle cerebral artery occlusion in control animals and patent middle cerebral arteries in TPA-treated animals. Serum fibrinogen and fibrin split products were unchanged in both groups, indicating the absence of systemic fibrinolysis. There were no intracerebral hemorrhages. It is concluded that, in this rat model, TPA increases blood flow with subsequent improvement in the EEG recording after thromboembolic stroke without evidence of systemic fibrinolysis. Intravenous TPA may be useful in the treatment of acute stroke in man.

Animals↗
PubMed1986

Ectopic pituitary adenomas with normal anterior pituitary glands.

Two patients with ectopic pituitary adenomas and biopsy-proven normal anterior pituitaries are described. Both tumors were located in the sphenoid sinus. One tumor produced prolactin, and the other one was a plurihormonal adenoma that produced predominantly adrenocorticotropin and to a lesser extent thyroid stimulating hormone and alpha subunit. The patient with the plurihormonal tumor, who had Cushing's disease, was cured by surgery while the patient with the prolactinoma was treated by surgery and medical therapy. A review of these two cases and an additional nine cases from the literature of ectopic pituitary adenomas in patients with normal intrasellar anterior pituitaries indicate that these uncommon tumors are capable of secretory function and may be the only cause of excessive pituitary hormone production.

Adenoma↗