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The concept of brain death has become important in law and medicine, replacing in some instances the concept of circulatory arrest as a definition of death. Yet, brain death has not been established as a clear clinical or pathologic entity, a point brought out here by comparison of criteria for identification. The need for more research is evident.

This report presents the results of a study using multiple techniques of the established human cell line, LM, which has been developed in culture medium from a patient with a right temporoparietal glioblastoma. This cell line has human subtetraploid karyotype and has several features of a transformed line in culture. These include continuous propagation for 10 years, ability to form tumor nodules when transplanted into immunologically suppressed hamsters, and pleomorphic appearance. Ultrastructurally, it is characterized by multiple nuclei, few actin cables, and numerous surface-membrane microvilli, as well as abundant 9- to 10-nm cytoplasmic filaments. By its immunological reactivity, the line can be shown to contain glial fibrillary acidic protein at low levels, consistent with its glial origin and continued nature. Dibutyryl cyclic adenosine monophosphate (db-cAMP) induces formation of long astrocytic-like processes as well. Its membrane electrical characteristics include a low resting membrane potential and short time constant. Used in a microtiter antiglioma antibody cytotoxicity assay, LM yields a positive reaction to antibodies in the sera of 80% of patients with astrocytomas and only 9% of normal blood-bank donors, suggesting that it shares common antigens with other astrocytic tumor lines. The varied characteristics of this glioblastoma-derived line emphasize the "multiforme" nature on the neoplasm and suggest that for characterization of any such line, multiple parameters are necessary to allow comparison with other long-term glioblastoma lines in the literature. The usefulness of the LM line in in vitro cell biological, immunological, chemotherapeutic, and radiobiological studies of gliomas makes such efforts very worthwhile.

Haematological indices in cord blood, measured by a Coulter Counter, in 50 mothers who smoked 10 or more cigarettes a day were compared with those in 75 control mothers who were non-smokers, but of similar age and parity. Smoking during pregnancy was associated with higher levels, of haemoglobin, and the haematocrit, as well as with higher red cell counts and a higher mean corpuscular haemoglobin. The percentage of fetal haemoglobin in cord blood was not affected by smoking. There was no correlation between social class and cord blood haemoglobin; but within social class groups, higher cord blood haemoglobin levels were associated with smoking. It is suggested that smoking during pregnancy stimulates fetal erythropoeisis.

Three models of human language processing can be discerned in contemporary neurobiology: the Wernicke-Broca model, primarily derived from studies of stroke and other brain lesions; the model developed by Dr. George Ojemann from electrical stimulation mapping of the cerebral cortex; and the linguistic model, evolved from Noam Chomsky's linguistic theories. The Wernicke-Broca model employs a posterior-sensory anterior-motor conception of brain language processing that is substantially different from the more modular conception developed from electrical stimulation mapping. The linguistic model attempts to explain language in terms of hierarchical mental function.

In the early development of American neurosurgical techniques, Harvey Cushing is often considered the founding father. As an accomplished artist and prolific writer his original operative sketches and detailed notes at the Peter Bent Brigham Hospital (1912-1932) are now being explored as early documentation of this pioneering surgeon's development of a field. We present four brain tumor cases with his unpublished sketches and direct quotations to illustrate both the trials and tribulations of those times and Cushing's innate surgical genius.

Astrocytomas, including glioblastoma multiforme, represent the most frequent and deadly primary neoplasms of the human nervous system. Despite a number of previous cytogenetic and oncogene studies primarily focusing on malignant astrocytomas, the primary mechanism of tumor initiation has remained obscure. The loss or inactivation of "tumor suppressor" genes are thought to play a fundamental role in the development of many human cancers. Thus, we have analyzed astrocytomas of various histological malignancy grades with polymorphic DNA markers to search for specific chromosomal deletions potentially pointing to loci containing tumor suppressor genes. Loss of constitutional heterozygosity indicating chromosomal loss or deletions was most frequently seen for markers on the short arm of chromosome 17 in 50% of the informative tumors (5 of 10 informative cases) and, to a lesser extent, for markers on chromosomes 1 and 10. Deletions on chromosome 17p were seen in both low-grade and high-grade malignant astrocytomas, suggesting that this chromosome may contain a tumor suppressor gene associated with the early events in tumorigenesis. The common region of deletions on the short arm of chromosome 17 is, therefore, clearly distinct from the gene causing von Recklinghausen neurofibromatosis (NF1), a tumor syndrome associated with glial tumors that maps to the long arm of chromosome 17. The search for progressively smaller deletions on chromosome 17p in astrocytomas may be the way to clone and characterize this locus, thus leading to insights into normal and abnormal growth and differentiation of glial cells.

Combining the power of stereotactic precision with open craniotomy in a stereotactic craniotomy technique decreases surgical time, morbidity, and postoperative hospitalization. Indications for its use are deep intrinsic masses 3.5 cm or less in diameter; small, superficial lesions otherwise difficult to localize; and lesions associated with motor, visual, or speech areas. Using the standard Brown-Roberts-Wells system allows a) precisely planned cortical entries, b) gross total lesion excisions under direct vision, c) use of probe-guided resection margins, d) small craniotomies through linear incisions, and e) use of local anesthetic alone for resections. The method and results of this universally available and relatively inexpensive technique are discussed in reference to 20 patients.

The authors report a study in which 109 cerebrospinal fluid (CSF) specimens from patients with varying neurological disorders were incubated in tissue culture medium for 1, 3, and sometimes 7 days. Strict criteria for malignancy were applied to cells found at these intervals. In 35 patients with verified central nervous system neoplasms, eight cases had malignant cells and 11 others had "doubtful" cells by tissue-culture analysis. Thirty-three of these cases were also examined with standard millipore cytological techniques: six had malignant cells and four had "doubtful" cells. Of 50 cases with inflammatory or other non-neoplastic conditions, cells were cultured in 13. None was considered malignant by our criteria. Tissue culture of CSF has several potential benefits. Even with stringent criteria, it is possible to demonstrate the presence of unequivocally malignant cells in CSF by tissue culture. The systemic application of such criteria may eventually increase the positive identification of malignancies. Further, since these cells are growing, the degree of malignancy may be more accurately determined by a study of growth in culture. Such a study could not be done by conventional methods. Finally, tissue culture can help to guide therapy in certain instances in which a surgical biopsy cannot be obtained.

Streptococcus sanguis 804 (NCTC 10904) was grown ih batch culture at constant pH. and the glucosyltransferase activity of the supernatant was assayed over a 40-h growth period. The optimum pH for enzyme production was 7.0 to 7.2. During growth of the culture, three reproducible phases of enzyme activity were observed. The polysaccharides synthesized during each of these phases were characterized as dextran-like glucans by analysis of acid hydrolysates, gas-liquid chromatography, and a specific aggregation technique. The glucans were studied further by infrared spectroscopy, enzymic degradation, and periodate oxidation. Differences in the proportions of alpha-(1 leads to 3)- and alpha-(1 leads to 6)-linkages were observed. The results suggest that glucan synthesis by S. sanguis involves a multienzyme system.

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.

A case of subdural tension pneumocephalus is presented. Computerized cranial tomography permitted rapid diagnosis including localization of the air, thus facilitating prompt treatment. Tension pneumocephalus should be considered in a patient with a cerebrospinal fluid drainage device who deteriorates after craniotomy.

The neuropeptides vasopressin, adrenocorticotropin (ACTH), and beta-endorphin seem to have important effects on memory and learning. Animal studies attempting to demonstrate these effects are difficult to interpret because of the complexity of behavior that is described as "learning" and the impossibility of assessing verbal learning in animals. This article therefore reviews some of the animal literature on neuropeptides and learning, but focuses primarily upon studies in humans, both in normal volunteers and in patients with neurological disorders. Vasopressin enhances learning under some conditions. Intranasal administration has been associated with improvement on psychometric tests in patients with mild Alzheimer's disease and Korsakoff's psychosis, although these findings are not uniform. It improves performance on memory tests in normal volunteers, but does not seem to improve the memory deficit after head trauma. Cerebrospinal fluid levels are low in patients with Alzheimer's disease. ACTH and melanocyte-stimulating hormone (MSH) are two peptides the primary behavioral effect of which seems to be on attention or goal-motivated behavior rather than on memory processes themselves. Visual discrimination and the ability to continue repetitive tasks are enhanced; in mentally retarded subjects, the administration of ACTH or MSH improves performance on a variety of neuropsychological tests. It does not, however, improve cognitive function in the elderly. Endogenous opioids including beta-endorphin and met-enkephalin seem to have primarily an amnesic effect in animal studies. Their role in human learning is still uncertain, although naloxone, which antagonizes their effects, has been associated with improved cognitive performance in patients with Alzheimer's disease. These data underscore the complexity of the processes associated with human memory and the rudimentary state of our present knowledge. Whatever the mechanisms, however, vasopressin, ACTH, and endogenous opioids seem to have important effects upon memory.

External pneumatic calf compression is effective but imperfect for antithrombotic prophylaxis in surgical patients. In preliminary studies, sequential filling of multisegmented leggings with graded pressure decreasing from ankle to knee increased venous flow velocity and wall shear stress, decreased residual venous volume, and enhanced postoperative fibrinolysis more than uniform compression. To determine if improved hemodynamics also increased antithrombotic activity, we performed a prospective randomized trial in neurosurgical patients comparing sequential application of graded pressure with uniform pressure applied to either a segmented bladder or to a single bladder. Deep vein thrombosis was diagnosed by leg scanning and impedance plethysmography and confirmed by phlebography. Venous thrombosis developed in 3 of 45 patients with graded-sequential filling, 6 of 50 with uniform compression-multiple compartments, and 3 of 41 with uniform pressure single bladder (differences not significant). These results suggest either that uniform compression offers all that can be expected of external pneumatic calf compression in prevention of venous thrombosis, or that even if a study with greater statistical power showed graded-sequential filling to be superior, the benefit/cost ratio of the more complex latter system is not likely to be large.

The experiments described herein use an in vitro preparation of choroid plexus to demonstrate that it is a vasopressin-responsive organ by morphologic criteria. Choroid plexus from rats was incubated for one hour in graded concentrations of arginine vasopressin (AVP). Within physiologic range of molar concentration, incubation in vasopressin induced a decrease in basal and lateral spaces in choroid plexus epithelial cells as well as an increase in number of dark cells. The number of cells with basal spaces decreased significantly from 82.7 +/- 9.2 in control tissue to 19 +/- 18 in tissue incubated in 10(-12) M AVP; similarly, the number with lateral cellular spaces decreased from 20 +/- 8.8 to 7.6 +/- 2.2 cells in 10(-10) M AVP. Dark cells increased in number from 3.8 +/- 2.6 in control conditions to 49 +/- 4 with 10(-9) M vasopressin. These data suggest important effects of arginine vasopressin in cerebrospinal fluid (CSF) on choroid plexus, compatible with enhanced fluid transport across choroid epithelial cells.

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.

This study evaluated the changes in pathways of cerebrospinal fluid (CSF) outflow that accompanied acute and compensated hydrocephalus in the rabbit. Intraventricularly injected 99mTc antimony sulfide was used as a tracer of outflow pathways, and specified structures were counted 12 to 24 hours after injection. Fifteen rabbits were divided into three groups: 1) an acutely hydrocephalic group in which 3 cisternal injections of blood were followed by a study of CSF pressure, ventricular size, and CSF outflow pathways 1 week after the last injection; 2) a control group treated according to the same protocol, except that sterile saline was injected instead of blood; and 3) a chronic group also treated according to the same protocol but in which the animals were maintained an average of 4 weeks after the last blood injection. Ventricular size was measured by computed digitation and expressed as an area ratio of ventricle to brain (VBR). In control animals, 11.8% of the injected colloid dosage was found in cranial perineural lymphatic channels, and 4.8% appeared in the spinal cord. The mean CSF pressure was 149 +/- 20.2 mm H20 (mean +/- SE) and the mean VBR was 0.040 +/- 0.003. In animals evaluated 1 week after subarachnoid injection, accessory cranial perineural lymphatic outflow decreased significantly to 3.4%, and spinal cord activity increased to 9.8% (P less than 0.05, two-tailed t-test). These animals were hydrocephalic and had CSF pressure of 247 +/- 25.1 mm H20 (mean +/- SE) and VBR of 0.083 +/- 0.009.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Acute mountain sickness (AMS) is usually a benign and self-limited illness that befalls previously healthy individuals who ascend rapidly to high altitude without sufficient acclimatization. In its more severe forms, AMS can progress to a life-threatening condition in which pulmonary or cerebral edema can occur singly or in concert. High altitude cerebral edema (HACE) is a little-known clinical entity that manifests itself by a perplexing array of both generalized and localized neurological symptoms and signs. Furthermore, the development of HACE in climbers offers a unique experimental situation in which to examine the effects of hypoxia on the central nervous system. The epidemiology and clinical picture of HACE are reviewed. In addition, the pathology and predominant pathophysiological mechanisms postulated to explain HACE are examined, and the present recommendations for the prevention and treatment of this dangerous and unusual form of brain swelling are discussed.

Ventriculitis developed suddenly in a patient with an undiagnosed abscess and was accompanied by obtundation, fever, meningismus, and hemiplegia. Aspiration of a streptococcal thalamic abscess and high doses of intravenous penicillin produced marked improvement. Increasing dysphasia 5 weeks later was accompanied by ventricular dilatation, most marked on the left, with no evidence of recurrent abscess. The left foramen of Monro was demonstrably patent. Shunting relieved the symptoms of aphasia; they recurred with one episode of malfunction of the shunt. This case lends support to the belief that parenchymal characteristics are important in hydrocephalus and demonstrates how asymmetrical ventricular dilatation can produce focal symptoms.

Opiopeptides may contribute to the pathophysiology of both endotoxic and hemorrhagic shock. To determine if endorphin secretion is similar in both types of shock, we divided 25 sheep into three groups: a saline control group (n = 10), an endotoxin-treated group (n = 9), and a hemorrhage group (n = 6). Each sheep had baseline determinations of mean arterial pressure (MAP) and plasma levels of beta-endorphin-like immunoreactivity (iB-EP). Experimental animals either received endotoxin (450 ng/kg intravenous) or underwent withdrawal of blood volume sufficient to diminish MAP by approximately one-third of baseline values. MAP and iB-EP levels were determined every 15 minutes thereafter for 5 hours. Individual data were averaged within each group and then compared between groups using analysis of variance. Both the endotoxin- and hemorrhage-treated groups showed a significant fall in MAP, which was significantly lower in the hemorrhage group than the endotoxin group. Endotoxin-treated animals displayed a mean peak iB-EP level 1,550% above baseline as compared to a mean peak iB-EP level of only 201% above baseline in the hemorrhage-treated group, despite a significantly greater degree of hypotension in the latter group; this difference in peak iB-EP response was significant. Mean peak iB-EP levels coincided with mean trough MAP values in the endotoxin-treated group while the mean peak iB-EP lagged the onset of mean trough MAP in the hemorrhage group. These results demonstrate that iB-EP secretory patterns differ in endotoxic versus hemorrhagic shock and suggest that distinct mechanisms of opiopeptide secretion accompany the two shock states.

Posttraumatic hydrocephalus is a treatable complication of head injury and can present with several different clinical syndromes. These include obtundation; simple failure to improve; a tetrad of psychomotor retardation, memory loss, gait trouble, and incontinence; and unusual symptoms including emotional disorder. Posttraumatic hydrocephalus seems to result from a blockage of cerebrospinal fluid (CSF) flow around the cerebral convexities. When the lumbar CSF pressure is consistently above 180 mm H2O, the hydrocephalus should be treated unless a contraindication to operation exists. Underlying brain injury from the trauma itself, however, may prevent recovery. When the typical symptoms of normal pressure hydrocephalus (NPH) are present, a shunt is also indicated. Decision-making is difficult when the patient has normal pressure, but is too injured to display the symptoms of NPH or has atypical symptoms. Overnight pressure recording, lumboventricular infusion testing, or cisternography may clarify whether a shunt is needed in this situation, but there is still considerable uncertainty about shunt prediction in this setting.

Men under 20 and over 50 years of age used a free walk-in clinic of the Navy more than women of the same age. Women 20-50 years old used it more than men in this age group. This appears to be a result of the distribution of Navy health care facilities in the study area. Teenagers used the clinic as much as patients over 50. Sore throat, skin rash, abdominal pain, earache, and backache were the five most common complaints (302 per 1,000 patients.) These complaints and 19 other problems were responsible for 822 patient visits per 1,000 in a study of 2,272 consecutive new patient visits. Eighteen percent of all visits were return visits for a specific complaint. An analysis of complaints by body system showed that 21.9 percent were otolaryngological, 18.8 percent musculoskeletal, 12.5 per cent gastrointestinal, 9.7 percent dermatological, 8.7 percent cardiopulmonary, 7.8 percent genitourinary, 9.0 percent general (fatigue, nervousness, malaise, or weakness), and 11.6 percent other system (neurological, hematological, and miscellaneous). These data indicate that a physician's time might be used more efficiently in a walk-in setting and that training for such a clinic must be different from traditional training for such fields as internal medicine.

A case of a subdural hygroma or chronic subdural hematoma of the thoracolumbar spinal meninges is described. This became symptomatic 9 years after trauma. Terminological ambiguity is discussed, along with the detailed clinical, radiological, and operative presentations of this rare condition.