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Biomedical subjects

N T Zervas

Publications and source records attributed to N T Zervas.

At least 73 records · Page 4Linked to original sources

Isovolemic hemodilution in experimental focal cerebral ischemia. Part 1: Effects on hemodynamics, hemorheology, and intracranial pressure.

A total of 76 splenectomized dogs were entered in a study of the value and effects of isovolemic hemodilution. Of these, seven were not included in the analysis because of technical errors. Of the remaining 69 dogs, 35 were treated with hemodilution; 28 were subjected to a 6-hour period of temporary occlusion of the distal internal carotid artery and the proximal middle cerebral artery, and seven underwent a sham operation only, with arterial manipulation but no occlusion. The other 34 dogs were not subjected to hemodilution; 26 of these underwent temporary arterial occlusion and eight had a sham operation only. In each group the animals were about equally divided into 1) an acute protocol with regional cerebral blood flow measurements by a radioactive microsphere technique and sacrifice at the end of the acute experiment, and 2) a chronic protocol with survival for 1 week to permit daily neurological assessment and final histopathological examination but without blood flow measurements. Isovolemic hemodilution was performed about 1 hour after the arterial occlusion or sham operation and was accomplished by phlebotomy and infusions of low molecular weight dextran to bring the hematocrit to a level of 30% to 32%. This treatment resulted in a very significant reduction in viscosity and fibrinogen levels. The decrease in hematocrit lasted throughout the week in the animals in the chronic protocol. The decrease in viscosity correlated almost linearly with the decrease in hematocrit. There was a slight decrease in systemic arterial pressure with hemodilution but there were no significant changes in central venous pressure or in pulmonary arterial or wedge pressure. There was a slight decrease in cardiac index in both the hemodilution and control groups, which may have been due to the effects of barbiturate anesthesia. There was a slight increase in the measured blood volume in both groups, which was probably artifactual and related to the method of calculation. Intracranial pressure increased significantly with time in all animals subjected to arterial occlusion, but this increase was less severe in the hemodilution group. There was no significant change in intracranial pressure in sham-operated animals, whether hemodiluted or not. The results of cerebral blood flow measurements, assessment of neurological conditions, and measurement of infarct size are given in Part 2 of this report.

Animals↗

Isovolemic hemodilution in experimental focal cerebral ischemia. Part 2: Effects on regional cerebral blood flow and size of infarction.

Seventy-six splenectomized dogs were entered in a study of the value and effects of isovolemic hemodilution. Of these, seven were not included in the analysis because of technical errors. Of the remaining 69 dogs, 35 were treated with hemodilution; 28 were subjected to a 6-hour period of temporary occlusion of the distal internal carotid artery and the proximal middle cerebral artery, and seven underwent a sham operation only, with arterial manipulation but no occlusion. The other 34 dogs were not subjected to hemodilution; 26 of these underwent temporary arterial occlusion and eight had a sham operation only. In each group the animals were about equally divided into 1) an acute protocol with regional cerebral blood flow measurements by a radioactive microsphere technique and sacrifice at the end of the acute experiment, and 2) a chronic protocol with survival for 1 week to permit daily neurological assessment and final histopathological examination but without blood flow measurements. The general experimental protocol, the hemodynamic and rheological measurements, and the changes in intracranial pressure are described in Part 1 of this report. In the animals with arterial occlusion, blood flow decreased significantly in the territory of the ischemic middle cerebral artery. This decrease was partially reversed by hemodilution in the animals so treated. When the changes in blood flow before and after hemodilution in treated animals are compared with the changes at equivalent times in animals without hemodilution, the increases in flow in the gray matter of the ischemic hemisphere brought about by hemodilution are statistically significant. The neurological condition of the animals in the chronic protocol (sacrificed 1 week after occlusion) with hemodilution, as evaluated by daily neurological assessment, was significantly better than that of the control animals. In the animals sacrificed acutely (8 hours after arterial occlusion), the volume of infarction as estimated by the tetrazolium chloride histochemical method was 7.36% of the total hemispheric volume in the control animals and 1.09% in the hemodiluted animals, showing a statistically significant difference (p less than 0.005). In the chronic animals these values were 9.84% and 1.26%, respectively (p less than 0.005), as calculated by fluorescein staining. By histopathological examination the volume of infarction in the chronic animals was calculated as 10.92% in the control animals and 1.20% in the hemodiluted animals (p less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Angiographic evidence of basilar artery constriction in the rabbit: a new model of vasospasm.

The main objective of this study was to produce angiographic evidence of basilar artery constriction using the rabbit model. The technique described involves the transdural injection of blood into the cisterna magna on two different days. The results obtained show that vasoconstriction occurs over a time period that is comparable in duration to that seen in patients undergoing vasospasm as a result of subarachnoid hemorrhage. Further investigation should be done to evaluate the usefulness of the rabbit model as a verifiable tool in studying the etiology of vasospasm.

Animals↗

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.

Adenoma↗

Lymphocytic adenohypophysitis of pregnancy with complete recovery.

A case of lymphocytic adenohypophysitis in a postpartum woman who became symptomatic during her 8th month of pregnancy is presented. The clinical presentation, endocrine findings, pathological findings, and operative management are discussed. Transient hypopituitarism is documented. Unlike most previously published cases, this woman had complete recovery of anterior pituitary function.

Adult↗

Incidence and management of complications of transsphenoidal operation for pituitary adenomas.

Two hundred fifty-five consecutive transsphenoidal procedures for pituitary adenomas were reviewed to evaluate complications and their management. There were no operative deaths. Cerebrospinal fluid (CSF) rhinorrhea was the most common complication, occurring in 2.7% of cases; diabetes insipidus was next, lasting less than 1 year in 1.6% of patients and over a year in 0.4%. Sinusitis occurred in 1.2% of patients, and delayed epistaxis occurred in 0.8%. Postoperative hematomas, meningitis, hydrocephalus, and deep venous thrombosis each occurred in 0.4% of cases. These results are discussed in the context of previous reports, including an international survey of pituitary surgeons. Although transsphenoidal surgery has a low morbidity and mortality, it is nevertheless associated with potentially serious difficulties that should be expeditiously recognized and managed.

Adenoma↗

Hormone production in clinically nonfunctioning pituitary adenomas.

Pituitary tumors in which no excess hormone secretion can be identified clinically have been considered as nonfunctioning or null-cell adenomas. Immunocytochemical data presented here suggest that many of these tumors contain subunits of the glycoprotein hormones. Of 160 patients referred for pituitary surgery, 37 (23%) had no evidence of excess hormone secretion on preoperative endocrine evaluation. Immunocytochemical staining of these tumors was carried out using antibodies specific for prolactin, growth hormone, adrenocorticotropic hormone, the beta subunits of luteinizing hormone (beta-LH), follicle-stimulating hormone (beta-FSH), and thyroid-stimulating hormone (beta-TSH), and the alpha subunit. One or more of these pituitary hormones were detected in 73% of cases. The alpha and beta subunits were detected most frequently, being found in 68% of cases; 27% had staining for one or more beta subunits and 37.9% had staining for both alpha and beta subunits. The incidence was: beta-FSH in 58%, beta-LH in 47%, beta-TSH in 33%, and the alpha subunit in 42%. Staining for multiple glycoprotein hormones was common (52%), and mixed glycoprotein hormones and prolactin cell types were found in 16% of cases. These data suggest that most apparently nonfunctioning pituitary tumors contain immunoreactive hormones and the majority of these are subunits of the glycoprotein hormones. Since the glycoprotein hormone beta subunits must combine with the alpha subunit to produce biologically active hormones, the production of the subunits alone may not have endocrine manifestations.

Adenoma↗

Clinically silent hypersecretion of growth hormone in patients with pituitary tumors.

Hypersecretion of growth hormone (GH) was found in three women aged 25 to 35 years old, with somatotroph adenomas without clinical stigmata of acromegaly. The patients had previously been diagnosed as having nonfunctioning pituitary macroadenomas, with extrasellar extension. Concentrations of GH were elevated preoperatively in all subjects and could not be suppressed during oral glucose tolerance testing. Somatomedin-C concentrations were elevated in two patients. Immunocytochemical studies of surgically obtained tumor tissue demonstrated sparse positive staining for GH in all subjects. Gel-chromatographic analysis of serum and tumor tissue samples demonstrated that the immunoactive GH was authentic GH. On pathological examination, the tumor was cellular in all cases, consisting of partly acidophilic and partly chromophobic cells. Electron microscopic analysis of one tumor showed a cell composition not previously described. These studies further characterize GH hypersecretion in a subset of patients with clinically nonfunctioning pituitary macroadenomas.

Adenoma↗

Comparison of the effect of fluosol DA and dextran 40 on regional cerebral blood flow, infarction size, and mortality in cats with temporary occlusion of the middle cerebral artery.

Twenty-four cats were divided into two groups and treated with an intravenous infusion of either fluosol DA or dextran. One-half of the animals in each group were ventilated with room air and one-half with 100% oxygen. The right middle cerebral artery was occluded for a period of 4 hours through a transorbital approach. Regional blood flow by the hydrogen clearance method was measured before and after the infusion of fluosol DA or dextran, after oxygenation in the animals on 100% oxygen, three times during the period of ischemia, and after reperfusion. Regional cerebral blood flow increased slightly with the infusion of fluosol or dextran, decreased slightly with hyperoxygenation in the animals so treated, and decreased markedly in the right hemisphere during temporary occlusion of the right middle cerebral artery in all groups. With reperfusion regional flows in the right hemisphere varied considerably, with some animals showing hyperperfusion and others essentially no flow. There was no significant difference in average regional cerebral blood flow between any of the groups. The severity of infarction in all groups was directly related to the decrease in regional cerebral blood flow in the right hemisphere during temporary occlusion. There was also a strong correlation between the regional cerebral blood flow in the right hemisphere after reperfusion and the severity of infarction. In general, the animals showing normal or increased flow after reperfusion had small infarcts and those showing no reflow had large infarcts. Mortality was high in all groups, was not significantly different between any of the groups, and was highly correlated to the size of infarction. In brief, in this study fluosol offered no advantage over dextran, and probably neither agent, in the dose used, offered any protection against cerebral ischemia.

Animals↗

Delayed CSF lavage for arteriographic and morphological vasospasm after experimental SAH.

Irrigation of the subarachnoid space after aneurysmal subarachnoid hemorrhage (SAH) has been reported to alleviate subsequent arterial vasospasm. The authors have investigated the effect of lavage of the cerebrospinal fluid (CSF) space in the two-hemorrhage canine model of vasospasm. Twelve dogs had basilar cistern lavage with 120 cc of artificial CSF 24 hours after each of two SAH's, and 12 control dogs had two sequential SAH's without intervening lavage of clot. The amount of clot on the ventral brain stem was evaluated at sacrifice and was graded from 0 (no clot) to 4 (maximum clot) to assess the adequacy of clot removal. Dogs that had undergone lavage had a median grade of 1 (range Grade 0 to 2); control dogs had a median grade of 2 (range Grade 1 to 3.5, p less than 0.001. Wilcoxon rank sum test), indicating significant reduction of gross clot by lavage. The neurological findings were graded from 0 to 5, based on meningismus, ataxia, paresis, and cranial nerve deficits. No significant differences in neurological grade were found on any day between the two groups. Satisfactory angiograms were obtained before and 7 days after hemorrhage and were controlled for blood pressure and blood gases; these showed significant spasm in both groups. There was a mean reduction (+/- standard deviation) of 21.6% +/- 16.2% in basilar artery diameter in control dogs, compared to a 28.8% +/- 15.1% reduction in dogs with lavage (difference not significant, t-test). There was a strong, but insignificant, trend toward reduction of endothelial desquamation in the basilar and middle cerebral arteries in dogs with lavage compared to control animals (p = 0.06). Corrugation and tearing of the elastica, thickened intima, intimal fibroplasia, vacuolization of the endothelial or smooth-muscle cells, and presence of blood cells in the adventitia occurred similarly in both groups. It appears that cisternal lavage 24 hours after hemorrhage in this model has no effect on the angiographic, neurological, or most morphological sequelae of SAH, in spite of evidence for removal of clot as seen at sacrifice. Any postulated interaction of clot and vessel resulting in chronic vasospasm must occur before this time. Evaluation of the effect of much earlier lavage (for instance, 1 hour after hemorrhage) may elucidate the point at which vasospasm is instigated after SAH, and help in determining what factors cause vasospasm.

Animals↗

Trigeminal projections to supratentorial pial and dural blood vessels in cats demonstrated by horseradish peroxidase histochemistry.

Anatomical and clinical observations suggest that supratentorial vascular structures contain afferent projections from the trigeminal ganglia. To characterize this innervation, horseradish peroxidase (HRP) and HRP conjugated to wheat germ agglutinin were applied to the pial and dural arteries and sinuses of 33 cats. HRP was restricted to the site of interest by applying it dissolved in a viscous polymer, polyvinyl alcohol (PVA), to achieve slow release and minimize diffusion. The ganglia of cranial nerves V, VII, IX, and X and the superior cervical ganglia (SCGs) were examined bilaterally for the presence of retrogradely transported protein. Horseradish peroxidase applied to the proximal middle cerebral artery was located in cell bodies occupying the portion of the ipsilateral trigeminal ganglion corresponding to the ophthalmic division and throughout both SCGs. When the tracer was applied to the right anterior or posterior superior sagittal sinus, HRP-positive cells were present as above, predominantly in the ipsilateral trigeminal ganglia corresponding to the ophthalmic division and throughout both SCG. When applied to the right middle meningeal artery, HRP was observed within neurons of ipsilateral SCG and in the ophthalmic division of trigeminal ganglia; a few enzyme-containing cells were present in ipsilateral regions corresponding to the second and third divisions. These observations support the concept that supratentorial vascular structures receive afferent nervous projections from trigeminal neurons.

Afferent Pathways↗

The microcirculation of cerebral arteries: a morphologic and morphometric examination of the major canine cerebral arteries.

A morphologic and morphometric examination of the major cerebral blood vessels in the dog was carried out to determine whether there were vasa vasorum in these arteries and what features might be associated with them. True vasa vasorum confined to the media were not seen in any of the vessels examined. Microvessels confined to the adventitia, however, were found in the internal carotid and vertebral arteries but not in the basilar, middle cerebral, or anterior spinal arteries. Animal size, vessel size as determined by adventitial and medial area, and the number of smooth muscle cell lamellae were not associated with the presence of these adventitial vessels; they occurred only in arteries with both an intra- and extradural portion. It therefore appears that most canine cerebral arteries do not have vasa vasorum.

Animals↗

Limitations of tetrazolium salts in delineating infarcted brain.

Tetrazolium 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.

Animals↗

Construction of experimental "giant" aneurysms.

Giant aneurysms were produced in dogs by initially producing a fistula between the common carotid artery and the external jugular vein. One week later the vein was ligated above and below the fistula to create a blind aneurysmal pouch. This model has been found useful in testing experimental techniques of aneurysmal obliteration by direct injection into the sac while the lumen of the parent vessel is temporarily protected by an endovascular balloon inflated at the neck of the aneurysm.

Animals↗

Gonadotropin and prolactin pulsations in hyperprolactinemic women before and during bromocriptine therapy.

Pulsatile gonadotropin secretion and its relationship to PRL and estradiol (E2) secretion were investigated in 20 hyperprolactinemic amenorrheic women by obtaining serial blood samples for 6- to 24-h periods. Thirteen patients were restudied in the early follicular phase of the menstrual cycle (days 3-5) after ovulatory periods were established during bromocriptine therapy. In the hyperprolactinemic women, the number of LH peaks ranged from 0-12/24 h, and LH peak amplitude ranged from 0-1.7 mIU/ml. Serum E2 correlated with mean LH concentrations (P less than 0.001) and LH pulse frequency (P less than 0.05), but not with LH pulse amplitude. FSH pulsations were identified in 3 of the 20 women. There was no correlation between mean FSH concentrations and either serum E2 or PRL. There was a significant correlation between LH and FSH concentrations (P less than 0.001). During bromocriptine therapy, with comparable E2 concentrations, 5 of the 6 patients studied with blood sampling every 20 min for 24 h had a significant decrease (P less than 0.01) in the number of LH peaks per 24 h, with no change in LH peak amplitude. Mean FSH concentrations were unchanged in bromocriptine-treated patients; however, there was a significant (P less than 0.02) decrease in FSH levels during sleep. Serum PRL was normal in all bromocriptine-treated patients, but normal PRL secretory patterns were not reestablished, and there was no correlation between LH pulsations and serum PRL concentrations. We conclude that 1) hyperprolactinemic women have a heterogeneous pattern of pulsatile gonadotropin secretion; 2) serum E2 correlates with LH pulse frequency but not pulse amplitude; 3) LH pulsations and PRL pulsations are asynchronous in hyperprolactinemic women before and during bromocriptine therapy; and 4) normal PRL secretory patterns are not required for ovulatory function in hyperprolactinemic women treated with bromocriptine.

Adenoma↗

Declaration of brain death in neurosurgical and neurological practice.

A survey of neurosurgeons and neurologists assessed physician practices in the declaration of brain death. Ninety-four per cent of the respondents thought that the diagnosis of brain death was legitimate; most thought that it was justified by a failure of somatic survival after brain death. Fifty-four per cent of the respondents had made the diagnosis themselves 1 to 5 times a year. The criteria used to make the diagnosis varied significantly among the respondents. Most required the absence of a pupillary reflex (88%), the absence of a corneal reflex (85%), a lack of ventilatory effort with disconnection of the ventilator (84%), and the absence of eye movements with head turning (80%). Fewer required an absent cough reflex (61%) or gag reflex (69%), dilated pupils (59%), a body temperature under 90 degrees F (56%), or a blood barbiturate level of zero (43%). Over 65% required an isoelectric electroencephalogram; 29% required only one, and 36% required two electroencephalograms 24 hours apart. Twenty-six per cent required absent deep tendon reflexes. The time required for the declaration varied from 6 to 24 hours. There was wide variation in the response to a hypothetical situation in which the family of a patient fulfilling brain death criteria did not want death to be declared. Seventy-eight per cent of the respondents would continue ventilatory support, although about a third of these would declare the patient dead while doing so. Only 6% would stop the ventilator despite the family's wishes. These results substantiate a wide variation in the actions of neurologists and neurosurgeons in brain death declaration. This has important implications for decisions about death in neurology and neurosurgery.

Attitude of Health Personnel↗

Modified crossed leg raising test and sciatica.

A modification of the crossed leg raising test has been helpful in identifying patients with intervertebral disc disorders. Simultaneous flexion of the neck and elevation of the contralateral leg produced pain in the ipsilateral (presenting) sciatic notch in five patients with either free fragments or herniated disc found at operation. All patients were symptom-free postoperatively.

Adult↗

Outcome 1 year after SAH from cerebral aneurysm. Management morbidity, mortality, and functional status in 112 consecutive good-risk patients.

A group of 112 consecutive patients who initially had no neurological deficits after subarachnoid hemorrhage (SAH) was followed intensively for at least 1 year. Ninety-four were in neurological Grade I or II (Hunt and Hess classification) on arrival. A hundred patients underwent late surgery but, despite excellent surgical results, major morbidity and mortality rates were observed related to preoperative complications. In the preoperative period, 14 (13%) rebled, 41 (37%) had symptomatic cerebral vasospasm, and 24 (21%) had hydrocephalus that required treatment. Of the 100 surgical patients, 73 were in Grade I or II, 26 in Grade III, and one in Grade IV. Six patients had intraoperative neurological complications, and two had delayed postoperative cerebral infarction. Six patients died during hospitalization, but only one as a result of operation. Six others died during the year following discharge of causes unrelated to the operation. The ultimate functional outcome at 1 year of these initially good-risk patients was poor. Only 46% were fully recovered, and 25% reported emotional or psychological disturbances that interfered with their daily lives. Forty-four percent could return to their previous jobs or a comparable position, and 20% obtained lesser employment. Management mortality at 1 year was 11%, and morbidity related to persistent neurological deficits (mainly strokes from vasospasm) was 20%. Thus, management mortality and morbidity at 1 year was 31%, and the number of patients returning to useful life was disappointing. The authors support the suggestion by previous workers that an analysis of at least the 6-month and perhaps the 1-year outcome (especially management mortality for all patients) provides the most important parameter for judging outcome and comparing different management protocols for SAH.

Activities of Daily Living↗