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Biomedical subjects

N T Zervas

Publications and source records attributed to N T Zervas.

At least 19 recordsLinked to original sources

Clonal origins of adrenocorticotropin-secreting pituitary tissue in Cushing's disease.

It is unclear whether Cushing's disease results from a primary pituitary disorder or arises in response to abnormal hypothalamic control of the pituitary gland. Clonal analysis can provide information as to whether neoplastic tissue is derived from a monoclonal proliferation of a genetically altered cell or from a polyclonal expansion of a group of cells affected by a common stimulus. We used X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase, hypoxanthine phosphoribosyltransferase, and DXS255 loci in 11 women with biochemically and pathologically confirmed Cushing's disease to determine the clonal origins of corticotroph adenomas and corticotroph hyperplasia. Tumor tissue from all 10 women with morphologically and immunohistochemically confirmed ACTH-secreting pituitary microadenomas demonstrated a monoclonal pattern. Pathologically confirmed corticotroph hyperplasia in a patient with a CRH-secreting bronchial carcinoid was found to be polyclonal. We conclude that corticotroph microadenomas in Cushing's disease are monoclonal, supporting the theory that a spontaneous somatic mutation is the primary pathogenetic mechanism in this disorder. In addition, the demonstration of polyclonality in corticotroph hyperplasia implies that excess of hypothalamic hormones is an etiologic mechanism in cases of Cushing's syndrome associated with ectopic CRH-secreting tumors.

Adrenocorticotropic Hormone

Somatostatin regulation of glycoprotein hormone and free subunit secretion in clinically nonfunctioning and somatotroph adenomas in vitro.

There is increasing evidence that clinically nonfunctioning pituitary tumors produce and secrete glycoprotein hormone and/or free alpha- and beta-subunits. In addition, hypersecretion of free alpha-subunit occurs in up to 37% of patients with somatotroph adenomas. An understanding of glycoprotein hormone regulation is important in developing effective therapeutic strategies for patients with tumors associated with intact glycoprotein hormone and free subunit hypersecretion. We investigated glycoprotein hormone and free subunit secretion by somatostatin in primary dispersed cultures of pituitary tumor cells from 23 patients with pituitary adenomas. Fifteen tumors from patients with clinically nonfunctioning adenomas (group 1) and 8 tumors from patients with somatotroph adenomas and cosecretion of alpha-subunit (group 2) were studied. Cultures were incubated with control or somatostatin-supplemented media for 24 h. Media samples from group 1 tumors were assayed for intact glycoprotein hormones and free alpha- and beta-subunits secretion levels, while media samples from group 2 cultures were assayed for alpha-subunit and GH secretion levels. Significant (P less than 0.05-0.001) inhibition of secretion of 1 or more intact hormones and/or free subunits was found in 10 of the 15 group 1 tumors. SRIF[10(-7) M] suppressed intact gonadotropin secretion in 60% of FSH-producing tumors and 30% of LH-producing tumors. Media concentrations of FSH beta and LH beta were decreased in 31% and 50% of group 1 tumors, respectively, following somatostatin treatment in those tumors which secreted free beta-subunits. alpha-Subunit was secreted by 12 of the 15 tumors, but significant (P less than 0.02-0.01) inhibition by somatostatin was observed in only 2 tumors. In contrast, significant (P less than 0.05-0.001) inhibition of alpha-subunit in the somatotroph adenomas was found in 6 of the 8 tumors. Significant decreases in alpha-subunit were observed only in those tumors where GH was also significantly inhibited by somatostatin. We conclude that 1) somatostatin inhibits intact glycoprotein or free subunit secretion in the majority of clinically nonfunctioning pituitary tumors in vitro and 2) alpha-subunit secretion is suppressed in 17% and 69% of clinically nonfunctioning and somatotroph adenomas, respectively, consistent with a differential regulation of alpha-subunit by somatostatin in these two tumor types.

Adenoma

Reduced incidence of cerebral ischemia following rupture of intracranial aneurysms.

A randomized study was carried out to determine if the administration of reserpine and kanamycin to lower the concentration of vasoactive biogenic monoamines would reduce the incidence of cerebral vascular ischemic complications and death following the rupture of intracranial aneurysms. Twenty-six treated and twenty-eight control (untreated) patients were studied. In the preoperative period, eight control (untreated) patients developed symptomatic cerebral ischemia as opposed to one treated patient. There was no correlation between the preoperative clinical findings of ischemia and angiographic evidence of vasospasm. In the post-operative period four control and one treated patient developed symptomatic cerebral ischemia; vasospasm, as demonstrated by cerebral angiography, paralleled these findings.

Cerebral Infarction

A telemetric pressure sensor for ventricular shunt systems.

A fully implantable telemetric differential pressure sensor has been developed which is incorporated with a shunt valve system. It is a unique single diaphragm device that allows in vivo confirmation of zero-point and pressure calibrations. The telemetry is implemented by a resonant circuit in the sensor and a radio frequency detector outside the body, and the in vivo pressure calibration is derived from a pressure-balancing method. The pressure sensor has been implanted with shunts in several patients, and is shown to be valuable both for measurements of intraventricular pressure and for determining proper function of hydrocephalus shunt valves and catheters.

Catheterization

Speech arrest in a dextral with a right mesial frontal astrocytoma.

A right-handed man had clustered groups of seizures characterized by speech arrest over a period of eight years. Later, speech arrest was accompanied by head-turning to the left and altered tone of the left limbs. An astrocytoma, centered in the right supplementary motor region, was identified. This case confirms the experimental data of speech arrest emanating from the right paramedian cortex of a right handed man.

Adult

Stereotactic radiofrequency hypophysectomy.

Clinical indications and technical details of RF hypophysectomy were reviewed. Evaluation of serveral hundred procedures toward pathologic and symptomatic amelioration ofmetastatic breast cancer and diabetic retinopathy, and also a few cases of intrasellar tumor, indicated sufficient benefit for endorsement in selected patients.

Breast Neoplasms

Prevention of deep vein thrombosis in neurosurgical patients: a controlled, randomized trial of external pneumatic compression boots.

A prospective, randomized clinical trial in 95 patients undergoing neurosurgical operative procedures was performed to investigate the efficacy of external pneumatic compression (EPC) of the calves as compared with results in a control group that received no specific form of prophylaxis for prevention of deep vein thrombosis (DVT). The diagnosis of DVT was established by the I125 fibrinogen scan and radiographic contrast phlebography. The data indicate that EPC provides significant protection against the development of DVT in comparison with results in the control group (p less than 0.005). There were no known pulmonary emboli in any of the EPC-treated patients. There were no complications of EPC.

Evaluation Studies as Topic

Decrease in neostriatal blood flow after D-amphetamine administration or electrical stimulation of the substantia nigra.

Local blood flow was measured in the caudate nuclei and, in some cases, other areas of rat and monkey brain by the hydrogen clearance technique. Resting values for caudate blood flow in the rat were similar to those reported elsewhere, i.e., 69 +/- 4 ml/min/100 g in the caudate. Administering D-amphetamine sulfate (0.5 mg/kg, i.p.) to rats reduced caudate flow by a maximum of about 33% after 30 min; this effect could be blocked by pretreatment with haloperidol (5.0 mg/kg, i.p.), a drug that blocks dopamine receptors. D-Amphetamine sulfate (1.5 mg/kg) also reduced caudate but not cortical blood flow in unanesthetized monkeys. Electrical stimulation of the pars compacta of the substantia nigra reduced ipsilateral caudate flow by about 25% without affecting flow in the contralateral caudate. This effect varied with the frequency and intensity of stimulation. These studies suggest that the intraparenchymal release of brain dopamine may modify intraparenchymal (local) blood flow.

Animals

A pressure-balanced radio-telemetry system for the measurement of intracranial pressure. A preliminary design report.

A fully implantable radio-telemetric differential intracranial pressure sensor is described with a zero-point calibration that can be confirmed repeatedly. Intracranial pressure (ICP) is measured with the device by the principle of applying a known external pressure to the scalp above the sensor and simultaneously detecting by radio-telemetry the zero-point of the sensor corresponding to a balance of pressures across it. The radio-telemetry is implemented by a resonant circuit in the sensor of which the resonant radiofrequency is detected outside the body. The sensor is passive, has built-in barametric compensation, negligible permeability of temperature drift, no calibration ambiguities, and fast dynamic response. The implanted sensor has been used successfully for short-term as well as long-term ICP monitoring. It has been implemented primarily for intermittent ICP measurements, but also adapted to continuous recording. Preliminary clinical experience with the system indicates that it is effective, safe, and simple to operate.

Electronics, Medical