Barnes Woodhall

Brain Adenosine Triphosphate: Decreased Concentration Precedes Convulsions

The concentration of adenosine triphosphate in the brain decreased before the onset of generalized convulsions in unanesthetized rats subjected to acute hypoxia or treated with hydroxylamine or pentylenetetrazole (Metrazol). As the convulsive episode continued, adenosine triphosphate decreased further. Stimulation of adenosine triphosphate production forestalled its disappearance from the brain and delayed the development of seizure activity.

Succinate: Protective Agent against Hyperbaric Oxygen Toxicity

When succinate is used to protect rats against the toxicity of oxygen at high pressure, 100 percent survive, with normal or above normal concentrations of adenosine triphosphate being present in the cerebral hemisphere, liver, and kidney. In contrast, 90 percent of the nonprotected animals died during exposure. In corresponding tissues of surviving nonprotected animals adenosine triphosphate concentrations are markedly reduced.

THE WELL-LEG-RAISING TEST OF FAJERSZTAJN IN THE DIAGNOSIS OF RUPTURED LUMBAR INTERVERTEBRAL DISC

The early history of the Lasegue sign has been reviewed, and credit is given to Fajersztajn for the first demonstration of the crossed or well-leg-raising test. Numerous observers have shown that flexion of the thigh on the abdomen with the leg extended causes rostral movement of the contralateral extradural nerve roots at the fourth and fifth lumbar and first. sacral levels, with approximation of these nerve roots to the anterior spine wall; these findings have been confirmed. It has been shown that approximately one-third of all Patients with verified disc protrusions have a positive well-leg-raising test, and that almost all of these have large protrusions. In the cases which this relationship has been studied, the disc protrusion has been found on the medial aspect of the affected nerve root.

Isolated perfusion in treatment of advanced carcinoma. Brain and face tumors.

From tbe Division of Neurosurgery, Duke University netted to one or both of the carotid arteries Medical Center, Durbam, Nortb Carolina. and juguIar veins. The perfusate used in the EGIONAL chemotherapeutic perfusions for R extracorporea1 circuit has been whoIe bIood or tumors of the brain and face were begun dextran. Anticancer agents used were nitrogen at Duke HospitaI in 1958, using an extracorpomustard (HNz), Arsg, Cytoxan,@ phenyIaIareaI pump-oxygenator-heat exchanger connine mustard, thio-TEPA, and severa amino

Effects of Hyperbaric Oxygenation on Metabolism I. ATP Concentration in Rat Brain, Liver and Kidney.

Summary 1) Tissue ATP concentrations were determined in the cerebral hemispheres, liver and kidney in rats exposed to air at 1 atmosphere, and to 100% oxygen for 2 hours at 1 and 3 atmospheres, and 1 1/2 hours at 5 atmospheres. 2 Liver and kidney had normal ATP levels at 1 atmosphere and increased ATP levels at 3 atmospheres (39% and 18% respectively). 3 Cerebral hemispheres had markedly depressed ATP concentrations at 1 atmosphere (57%) and 3 atmospheres (34%). 4 Significant decreases in ATP levels occurred in cerebral hemisphere (54%), liver (44%), and kidney (63%) of rats exposed to 100% oxygen for 1 1/2 hours at 5 atmospheres. 5 The significance of the findings is discussed.

Protection of brain metabolism with glutathione, glutamate, gamma-aminobutyrate and succinate.

Studies on protective agents in oxygen toxicity experiments led us to believe that a glutathione (GSH)-glutamate-γ-aminobutyrate (GABA)-succinate pathway may serve as a secondary support system in the maintenance of brain energy levels (adenosine triphosphate [ATP] concentration). This “shunt” is shown in Fig. 1. The glutamate-GABA-succinicsemialdehyde-succinate shunt is a well established pathway (1-8) to which no major physiological significance has been attached. The GABA-succinate shunt has been suggested as a means of metabolizing GABA (9, 10). It has also been reported to function as a means of bypassing inhibition of the alpha-ketoglutarate dehydrogenase system of the citric acid cycle by withdrawal of alpha-ketoglutarate from the cycle by transamination with GABA to yield glutamate and reentry of the carbon chain of GABA into the cycle at the succinate level (9, 10). The possible physiological importance of the shunt is seen if one recognizes that succinate markedly stimulates respiration and oxidative phosphorylation. Krebs et al. (11) reported that succinate oxidation can monopolize the respiratory-electron transport chain which is the major source of ATP production. Sanders et al. (12, 13) observed significantly higher respiration rates with succinate in brain, liver, and kidney of rats when compared with alpha-ketoglutarate and glutamate. Data shown later indicate that succinate stimulates brain respiration and oxidative phosphorylation in the mouse, rat, guinea pig, rabbit, cat and dog. The factor limiting the amount of succinate available for metabolism has generally been considered to be the rate at which alpha-ketoglutarate is converted to succinate by enzymes of the Krebs cycle. Roberts (8) showed that conversion of GABA to succinate by GABA transaminase is rapid, and that both glutamic acid decarboxylase and GABA transaminase have pH optima (6.5 and 8.2, respectively) such that small changes in intracellular pH—within the physiological range—could result in large changes in these enzyme activities in situ (8, 14, 15).

Localized Cerebral Hypothermia.

Conclusion Localized cerebral hypothermia has been produced in the dog by an extracorporeal circulation utilizing the carotid arteries and external jugular veins. During the acute stage of perfusion, various parameters of study have been recorded and in general, these results are in accord with those noted in states of generalized hypothermia. Survival is predicated upon low perfusion flows and development of perfusion pressure closely aligned with the systemic arterial pressure. Such long-term survivals allow the further investigation of the effect of various drugs and chemical substances upon the normothermic and hypothermic brain whose circulation is isolated in a measurable manner from the systemic circulation.

The effects of normal cerebrospinal fluid on blood clotting and fibroblast growth.

Summary In 50 normal CSF samples, no thrombin, fibinogen, prothrombin, proconvertin, proaccelerin, antihemophilic globulin or thromboplastin activity was found. These samples had no effects different from those produced by artificial control solutions on the coagulation time of a thrombin-fibrinogen system, and they demonsrated no fibrinolytic activity. In addition, they had no effect on chick fibroblast growth. There is no idication from these results that CSF specifically interferes with the healing of ruptured intracranial aneurysms.

Rapid Method of Metabolically Characterizing Individual Tumors.

Summary A rapid method for biochemically characterizing individual neoplasms particularly in relation to amino acid content and requirements is described. It is suggested that use of this method will facilitate the more accurate choice of chemotherapeutic agents in treatment of individual tumors even of the same morphologic class, and perhaps be an effective means of rapidly screening metabolic antagonists as to their effect upon individual tumors.

Acetylcholine Esterase Content of Brain Tumors

The acetylcholine esterase content of 50 brain tumors, and of 13 brain lesions not neoplastic in character, has been determined by the pharmacological method previously described. 1 All material was obtained immediately following removal in the neurosurgical operating room. The tissue to be examined for acetylcholine esterase content was exposed to the action of no drugs. The acetylcholine esterase activity (Q.CHE.) was determined as the number of milligrams of acetylcholine iodide hydrolized by 100 mg of tissue dry weight in one hour at 37°C and pH 7.61. The histologic or pathologic structure of the tissue resected at operation and examined for Q.CHE. content was established by multiple sections, fixed in Cajals formalin-ammonium-bromide solution, and after the appropriate time of fixation stained with, (1) Penfields second modification of Rio-Hortegas silver sodium carbonate stain, (2) Rio-Hortegas silver lithium carbonate stain, and (3) Cajals gold chloride sublimate method. Other material fixed in Zenkers fixative was stained with hematoxylin and eosin and with phosphotungstic hematoxylin. As indicated in Table I, 8 tumors of the astroblastic and astrocytic types occurring in the cerebellum had an average Q.CHE. of 18.8. One tumor of this type occurring in the cerebrum had a Q.CHE. of 18.2. but 2 others listed as astrocytomas had a Q.CHE. of 0.8 and 1.9 respectively. However, these last 2 were clearly of a different histologic character from the first and may very well be examples of what Scherer 2 refers to as “malignant dedifferentiation of an astroblastoma into a glioblastoma.” Histological diagnosis in such cases is notably difficult and uncertain. It is also ot interest to recall to that a significant clinical difference is recognized between the astrocytomas of the cerebrum and those of the cerebellum. Tumors of the astroblastic and astrocytic type occuring in the cerebellum are found chiefly in the children and young adults.