Raymond A. Clasen

Vital staining, serum albumin and the blood-brain barrier.

Vital staining was studied by quantitating the amounts of Evans blue and serum albumin in muscle and in abnormal brain. On the basis of differences in the ratio of dye to albumin in tissue and in serum, it was concluded that the coloration of tissue involves both the presence of serum albumin in tissue and the binding of dye not associated with serum albumin by tissue. The mode of binding of free dye by edematous cerebral tissue was studied by comparing the chemical structures of a series of acid dyes which did and did not function as vital stains. It was concluded that substantivity for edematous cerebral tissue requires the presence on the dye molecule of paired widely separated electron-donating hydrogen bond forming groups placed away from the solubilizing acid groups. It is suggested that the primary mode of binding for Evans blue in tissue is through the formation of hydrogen bonds between the azo groups of the dye and the hydroxy groups of tissue polysaccharides. These findings are conceptually related to the blood-brain barrier in that the presence of staining in the brain reflects the presence of increased amounts of albumin either at the time of observation or at some time in the past.

Furosemide and pentobarbital in cryogenic cerebral injury and edema

The effects of furosemide and pentobarbital on the edema associated with cryogenically-induced cerebral lesions in the rhesus monkey were quantitatively measured. Both drugs caused a decrease in the increments of water, sodium, and chloride in the damaged hemisphere. In addition, the pentobarbital was associated with a decrease in the uptake of serum protein. The effects of the two drugs were not additive. It is proposed that furosemide be given a clinical trial in the treatment of human cerebral edema.

Magnetic resonance imaging as a sensitive and specific predictor of neoplasms removed for intractable epilepsy.

Summary: Twenty‐three patients had magnetic resonance imaging (MRI) and computed tomography (CT) of the head prior to surgery for medically intractable epilepsy. Eleven patients had neoplasms, mostly astrocytomas. Six of the 11 tumors were seen on CT. In five of the six cases, the MRI showed a focal area of increased signal on T2‐weighted images. All 11 tumors were detected by MRI. None of the non‐neoplastic lesions produced an abnormal T2‐weighted signal area on MRI. Only one of the non‐neoplastic lesions was seen on both CT and on MRI. MRI allowed clear discrimination between tumors and non‐neoplastic lesions in patients coming to surgery for intractable epilepsy.

The Chemistry of Isolated Edema Fluid in Experimental Cerebral Injury

Focal areas of hemorrhagic necrosis were produced in the brains of anesthetized dogs by a freezing technique which has been described in previous publications (Clasen, et al., 1953). Briefly, this consisted of the application of a freezing instrument cooled by liquid nitrogen to the exposed intact skull. The instrument was left in place for five–ten minutes. This resulted in a circumscribed lesion involving both gray and white matter in the underlying brain. In the first hour after injury, cellular damage was restricted to the lesion. Four hours after injury, histologic evidence of edema was seen both in the lesion and in the adjacent white matter. Both areas showed positive staining by the periodic acid-Schiff (PAS) technique (Clasen, et al., 1957).

Recurrent intracranial epithelioid hemangioendothelioma associated with multicentric disease of liver and heart: case report.

Epithelioid hemangioendothelioma is an unusual vascular neoplasm with prominent cytoplasmic vacuolization representing primitive lumen formation. A case is presented of this unique vascular neoplasm in a woman with a seizure disorder who had cardiac, hepatic, and recurrent nervous system lesions. To our knowledge, this is the third known case of intracranial epithelioid hemangioendothelioma. Emphasis is placed on the indolent course of this rare neoplasm, with a recommendation for aggressive surgical treatment and diligent follow-up.

Adenocarcinoma metastatic to a growth-hormone-secreting pituitary adenoma: Case report

Although the pituitary gland is known to harbor metastatic deposits, it is a rare occurrence for a metastatic deposit to appear in a pituitary adenoma. A case is presented of an adenocarcinoma metastatic in an acromegalic patient with a pituitary adenoma. This report adds to the literature of the unusual phenomenon of neoplasm-to-neoplasm metastasis.

Protein and electrolyte changes in experimental cerebral edema.

Analysis of protein and electrolyte data in cryogenic cerebral edema in the rhesus monkey has led to the conclusion that, in the first 24 hours (h) after injury, the edamatous process is not homogenous, but compartmentalized. This involves, first of all, a division into intra- and extracellular compartments. The intracellular compartment is further divided into a compartment containing water, electrolytes, and serum proteins, and a compartment containing only excess sodium. The extracellular compartment is also subdivided into a compartment containing albumin, globulin, and electrolytes, and a compartment containing only albumin and electrolytes. Anatomically, the latter is most likely the pre-existing normal extracellular space

The Staining of the Myelin Sheath by Luxol Dye Techniques

The basic mechanisms by which luxol fast blue stains myelin sheaths was studied by experiments directed to elucidating the chemistry of the dye, the nature of the substrate, and the mode of binding of the dye to the substrate. The diphenylguanidine salts of a series of acid dyes were synthesized. All functioned as myelin stains demonstrating that the chemical basis of the staining reaction is the fact that luxol fast blue is the diarylguanidine salt of an acid dye and is not related to the specific structure of the dye. The nature of the substrate was investigated by chemical analysis of isolated myelin and tissue sections. It was determined that myelin contains a high proportion of non-polar amino acids and fatty acid residues which are not extractable by lipid solvents. It is suggested that these structures are concentrated in hydrophobic sites in the myelin substrate and that the dye gains access to these by virtue of its water insolubility. The mode of binding was studied by chemical analysis of the diphenylguanidine salt of congo red in its reaction with tissue sections. It was determined that when the dye is bound to the substrate the diphenylguanidine is released. Since with all luxol dyes the shade of the myelin sheath changes following the application of the basic counterstain, it is further proposed that these dyes have a double function in this staining reaction acting as both dyes and mordants.

Silent corticotroph adenoma: case report and literature review.

OBJECTIVE To review the initial clinical manifestations and diagnosis of silent corticotroph adenoma. METHODS We report a case and summarize the relevant literature. RESULTS A 52-year-old patient with hypopituitarism underwent resection of a silent corticotroph adenoma. A circulating species was detected postoperatively, reactive in a highly sensitive adrenocorticotropic hormone (ACTH) 1-39 immunoradiometric assay (IRMA) and beta-endorphin or beta-lipotropin radioimmunoassay. The basal morning cortisol concentration consistently was <10 microg/dL. Dynamic testing was performed to screen for Addisons disease, congenital adrenal hyperplasia, and Cushings syndrome. During dexamethasone suppression, the molar concentration of circulating ACTH precursors by a two-site IRMA was 55-fold greater than the concentration of ACTH 1-39 by IRMA. We concluded that the tumor displayed impaired processing of pro-opiomelanocortin (POMC) and secreted a bioinactive POMC-derived peptide that was reactive in the ACTH 1-39 IRMA. CONCLUSION Patients with silent corticotroph adenoma do not have clinically evident Cushings syndrome. In some cases, bioinactive ACTH precursors may be detected by a sensitive ACTH 1-39 IRMA.

Computed Tomography of Vasogenic Cerebral Edema

The vasogenic cerebral edema associated with four different types of human lesions was studied by correlating the CT scan with the histologic pattern. The cerebral edema associated with cryogenic lesions in the rhesus monkey, considered to be the prototype of vasogenic edema, was also studied. It was concluded that the areas of diminished density observed around these cerebral lesions represents histologically recognizable cerebral edema. The density of this edematous tissue varied from 11 to 17 H. It was further concluded that these differences in density may be a reflection of the protein content of the edema fluid.