Nicholas T. Zervas

Clinically nonfunctioning pituitary tumors are monoclonal in origin

Clinically nonfunctioning pituitary adenomas are benign neoplasms comprising approximately 25-30% of pituitary tumors. Little is known about the pathogenesis of pituitary neoplasia. Clonal analysis allows one to make the important distinction between a polyclonal proliferation in response to a stimulatory factor versus a monoclonal expansion of a genetically aberrant cell. We investigated the clonal origin of pituitary tumors using X-linked restriction fragment length polymorphisms at the phosphoglycerate kinase and hypoxanthine phosphoribosyl-transferase genes. Restriction enzymes were used to distinguish maternal and paternal X-chromosomes, and combined with a methylation-sensitive restriction enzyme to analyze allelic X-inactivation patterns in six pituitary adenomas. All six tumors showed a monoclonal pattern of X-inactivation. These data indicate that nonfunctioning pituitary adenomas are unicellular in origin, a result consistent with the hypothesis that this tumor type is due to somatic mutation.

Decreased Bone Density in Hyperprolactinemic Women

HYPERPROLACTINEMIA is a relatively common clinical problem, occurring in more than 25 per cent of women who present with secondary amenorrhea.1 , 2 Amenorrhea, anovulation, and galactorrhea are wel...

Long-Term Mortality after Transsphenoidal Surgery for Cushing Disease

Survival of patients treated for Cushing disease with current management techniques between 1978 and 1996 was better than the poor survival historically associated with this disorder.

Limitations of tetrazolium salts in delineating infarcted brain

SummaryTetrazolium salts, histochemical indicators of mitochondrial respiratory enzymes, have been used by some pathologists to detect infarcts in myocardium. We explored the utility of this technique in detecting experimental brain infarcts and report our findings. Infarcts were produced in cats, gerbils, and rats by unilateral temporal and permanent cerebral vessel occlusion. After various time periods the animals were killed, and their brains were reacted with 2,3,5, triphenyl, 2H-tetrazolium chloride (TTC). The experimental and contralateral hemispheres were examined by light and electron microscopy. The TTC-stained tissue was correlated with histology. In some situations the histological condition of the tissue correlated well with the TTC staining results. Brain regions supplied by temporarily occluded vessels and judged infarcted by light and electron microscopy did not stain. In these regions less than 6% of the mitochondria were intact. In brain tissue from animals with permanent vessel occlusion (no reflow) mitochondria were intact despite the fact that other cellular organelles, such as nuclei, were destroyed. TTC stained such mitochondria and as a result could not distinguish infarcted brain in complete ischemia situations (no reflow). Another draw back to this staining procedure was 36 h after infarction macrophages with intact mitochondria would replace damage neurons and be stained. Under ideal conditions though this technique can detect irreversibly damaged brain as early as 2.5 h after artery occlusion.

Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas.

Approximately 25% of patients with pituitary adenomas have no clinical or biochemical evidence for excess hormone secretion and are classified as having null cell or nonfunctioning adenomas. To characterize the cell type of these tumors, we analyzed pituitary hormone gene expression in clinically nonfunctioning pituitary adenomas using specific oligonucleotide probes for the messenger (m)RNAs encoding growth hormone, prolactin, ACTH, and the glycoprotein hormone subunits, alpha, luteinizing hormone (LH)beta, follicle-stimulating hormone (FSH)beta, and thyroid-stimulating hormone (TSH)beta. Expression of one or more of the anterior pituitary hormone genes was found in 12/14 (86%) of the patients with clinically classified nonfunctioning adenomas. Expression of one or more of the glycoprotein hormone genes (alpha, LH beta, FSH beta, TSH beta) was identified most commonly (79%) with expression of multiple beta-subunit genes in many cases. Expression of alpha-subunit mRNA was found in each of the adenomas from patients expressing one of the beta-subunit mRNAs and in three patients with no detectable beta-subunit mRNA. Although FSH beta and LH beta mRNAs were found with similar frequencies in nonfunctioning adenomas, expression of FSH beta mRNA was generally much more abundant. TSH beta mRNA was detected in only one adenoma. The levels of glycoprotein hormone subunit mRNAs were variable in different adenomas, but the lengths of the mRNAs and transcriptional start sites for the alpha- and beta-subunit genes were the same in the pituitary adenomas and in normal pituitary. Growth hormone and prolactin gene expression were not observed in the nonfunctioning adenomas, but ACTH mRNA was found in a single case. Immunohistochemistry of the adenomas confirmed production of one or more pituitary hormones in 13/14 (93%) nonfunctioning tumors, with a distribution of hormone production similar to that of the hormone mRNAs. These data indicate that pituitary adenomas originating from cells producing glycoprotein hormones are common, but are difficult to recognize clinically because of the absence of characteristic endocrine syndromes and defective hormone biosynthesis and secretion.

Idiopathic spinal cord herniation: a treatable cause of the Brown-Sequard syndrome--case report.

Symptomatic herniation of the spinal cord through the dura is an uncommon clinical problem. Since 1989, we have encountered three patients who each presented with an unexplained, longstanding Brown-Sequard syndrome and were found to have idiopathic herniation of the thoracic spinal cord. This report describes the clinical, radiographic, and surgical findings in these three patients and reviews the five previously reported patients with this syndrome. Idiopathic herniation of the spinal cord is a treatable cause of the Brown-Sequard syndrome that may be more common than is currently recognized and should be known to all surgeons managing spinal disorders.

A Mobile Computed Tomographic Scanner with Intraoperative and Intensive Care Unit Applications

INTRODUCTION A mobile computed tomographic scanner has been developed in which the scan plane is selected by means of gantry translation, rather than by translation of the patient table. This permits computed tomographic scanning in situ of any patient who is positioned on a radiolucent surface that fits within the inner diameter of the gantry. We report the design of and initial experience with this scanner as used with adapters for intraoperative and bedside computed tomography (CT). METHODS The scanner is equipped with wheels, draws power from wall outlets (120 V, 20 A) in combination with batteries, and has a translating gantry. Preclinical studies of image quality were performed with phantoms. An operating table adapter was built for use with a radiolucent cranial fixation device. A bedside adapter was built that holds the head and shoulders of a patient in the intensive care unit. RESULTS The preclinical phantom studies showed satisfactory image spatial resolution (0.8 mm) and low-contrast resolution signal-to-noise relative standard deviation (0.37%). Experience to date with 12 patients has confirmed the feasibility of intraoperative CT on demand. Experience to date with 26 patients has confirmed the feasibility of routine bedside CT in the intensive care unit. CONCLUSION With these adaptations, mobile CT may increase the efficiency of intraoperative scanning by making it available to multiple operating rooms without committing it to any room for an entire operation and may increase the efficiency and safety of CT of critically ill patients who currently need to leave the intensive care unit to travel to a fixed CT installation and back.

Brain H3‐catecholamine metabolism in experimental cerebral ischemia

Unilateral ligation of a common carotid artery in gerbils causes a major depletion of brain dopamine, which is most marked in brain regions known to receive dopaminergic projections. To determine whether this depletion reflects release of stored dopamine, a radioactive label (H3-dopamine) was introduced into brain dopamine pools 4 hours prior to ligation. Twenty-four hours later, brain H3-catecholamines were profoundly depressed ipsilateral to the lesion among animals exhibiting clinical signs of stroke. Within brain regions known to receive dopaminergic projections, common carotid ligation also was associated with a selective decrease in the concentration of H3-deaminated metabolites. These data suggest that cerebral ischemia is associated with release of catecholamines, as well as with impaired oxidative metabolism of catecholamines.

A Model for Experimental Cerebral Arterial Spasm

Vasospasm of the basilar artery of the dog was induced by subarachnoid injection of arterial blood through the cisterna magna. Cerebral angiography was employed to evaluate quantitative assessment of the spasm. Chronic vasospasm was successfully induced in 100% of surviving dogs. Biphasic vasoconstriction was observed. The acute phase occurred within 30 minutes after the blood injection and tended to abate. Chronic spasm was demonstrated on the second days angiograms and persisted to the seventh day in some cases. Etiology of the chronic spasm using this model is now under investigation. Vasospasm was not due to alterations in blood gas concentration or blood pressure, to increased CSF pressure or to injury from contrast medium or direct trauma. The primacy of blood as the offending agent is strongly suggested.

Combined Approach to “Dumbbell” Intrathoracic and Intraspinal Neurogenic Tumors

The unexpected finding of an extension of a neurogenic tumor from the thorax through the spinal foramen into the neural canal complicates its removal. Serious neurological complications may result from a two-stage approach, whether done first through the thorax or neural canal. Vertebral tomography or computed tomographic scanning reveals enlargement of a spinal foramen in advance of operation. Myelography confirms the probable presence of an intraspinal component. Four patients have been operated on using an approach designed to allow wide posterolateral thoracotomy and concomitant laminectomy for single-stage removal of the entire tumor. In 3 patients the diagnosis was schwannoma and in 1, neurofibroma. All had good results.