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Biomedical subjects

G M Hochwald

Publications and source records attributed to G M Hochwald.

At least 37 records · Page 2Linked to original sources

Enkephalin-induced changes in ventilation and ventilatory pattern in adult dogs.

We studied the changes in ventilation induced by intracisternal administration of enkephalins in four unanesthetized adult dogs. Instantaneous minute ventilation (VT/TT) decreased markedly after D-Ala-Met-enkephalinamide (DAME). Mean VT/TT decreased maximally by 20-50 min after DAME and lasted an additional 15-60 min; by 2 h, VT/TT had returned to base line. Four doses (5, 25, 60, and 125 micrograms/kg) of DAME were used, and the ventilatory response depended on the dose. Mean inspiratory time decreased but mean expiratory time and mean TT showed a marked prolongation. Periodic breathing (2-3 breaths separated by long apneic pauses) occurred in every study and the frequency of sighs increased considerably. All these ventilatory changes were reversed by low doses of naloxone or naltrexone; in addition, VT/TT increased well above base line after the administration of these antagonists. However, naloxone did not increase VT/TT when injected without prior administration of DAME. We conclude that 1) the decrease in VT/TT is due to a decrease in respiratory duty cycle; 2) periodic breathing and increased frequency of sighs constitute part of the changes in the ventilatory pattern induced by DAME; 3) a ventilatory withdrawal reaction may occur after a receptor-agonist interaction of short duration; and 4) although enkephalins can modulate ventilation and the breathing pattern in a major way, these data provide no evidence suggesting that this modulation is tonic.

Animals↗

Pressure-absorption responses to the infusion of fluid into the spinal cord central canal of kaolin-hydrocephalic cats.

The resistance to cerebrospinal fluid (CSF) absorption through the alternative CSF absorption pathway in kaolin-induced hydrocephalic cats was measured by the constant infusion-manometric test. The cerebral ventricles were bypassed, and artificial CSF was infused directly into the central canal of the spinal cord. The infusion rates were increased stepwise from 0.022 to 0.168 ml/min when the capacity to absorb CSF was exceeded. There was an initial increase in resistance which was associated with the emergence of infusion fluid through a slit-like opening in the dorsal columns of the lower lumbar spinal cord. The resistance to flow decreased when the infusion rate was greater than 0.086 ml/min. Fluid accumulated in the spinal subarachnoid space when the ability to absorb was exceeded. The diversion of this fluid caused the pressure in the spinal cord central canal to fall rapidly. The results suggest that the CSF absorption deficit in chronic kaolin-induced hydrocephalic cats is probably caused by the restriction of CSF flow from the central canal through the spinal cord and into the spinal subarachnoid space. As a result of kaolin, the central canal is sufficiently dilated to permit, during infusion, the flow of at least five times as much CSF as the hydrocephalic cats produce. It is not clear whether the overloading of the CSF absorption mechanism is due to the restrictions imposed by the size of the subarachnoid space, or to the structures in this space involved with the return of CSF to the blood.

Absorption↗

A study of reactions to Corynebacterium parvum (C. parvum) in the brain and dermis of the rat.

A comparative analysis was made of the histological changes caused by Corynebacterium Parvum (C. parvum) infected into the brain and dermis of normal and C. parvum presensitized rats. Control rats were injected with saline. It was shown that for approximately 3 days after the intracerebral injection the brain reacted with a polymorphonuclear cell infiltration. This reaction was replaced in order by lymphocytes, macrophages, and finally by epithelioid cells progressing to granuloma. The histological changes were similar but more intense in the dermis than in the brain. Lymphocytes reached a peak by day 7, macrophages by day 3, and epithelioid cells by day 18. In comparison to the dermis, the cellular infiltration in the brain is more delayed, less intense and of longer duration. Intracerebral saline induced a moderate lymphocytic infiltrate, and in C. parvum presensitized rats a more intense macrophagic response. It is concluded that the brain of the rat, especially in presensitized animal, mounts an inflammatory response to C. parvum which is morphologically similar to that seen in the skin.

Animals↗

Derivation of transplantable 7,12-dimethylbenz[a]anthracene-induced chicken fibrosarcoma lines: differences in metastasizing properties and organ specificity.

Several transplantable 7,12-dimethylbenz[a]anthracene-induced SC chicken fibrosarcoma (CHCT-NYU) lines were studied for their ability to grow in internal organs after iv injection (artificial metastases) into 1- to 3-week-old chickens. Some tumor lines were recently derived, whereas others were studied after many serial subcutaneous transplantations. STriking similarities as well as differences were found between tumor lines' ability to grow in various organs. Artificial metastases were seen primarily in the stomach, pancreas, lungs, heart, and muscle, and occasionally also in the kidneys and in the liver. Agammaglobulinemic recipients showed more extensive organ involvement than normal recipients of the same age. Whole-body gamma-irradation also enhanced the incidence of artificial metastases, particularly in lungs. Antibody from the serum of a primary tumor-bearing host reduced the growth of the corresponding tumor in many organs. The metastatic pattern of line CHCT-NYU4 was a relatively stable property, since there was little difference in the internal localization of these tumor cells studied before and after 15 serial subcutaneous transplants. However, intravenous transplantation of tumor cells from line CHCT-NYU4 taken from the liver, lungs, and pancreas of a single recipient established sublines with changes in organ specificity. After a few such serial transplants of liver-derived tumor, a line was derived that grew virtually in the liver alone. A subline with preference for growth in lungs was also obtained, but its ability to grow in the pancreas persisted. A pancreas-derived tumor line also grew in the liver and lungs. Subcutaneous transplants of tissue fragments of the lung-derived tumor line caused the appearance of spontaneous metastases in lungs. The incidence of spontaneous metastases with the lung-derived line was much greater than that with the liver-derived line or with the original CHCT-NYU4 line.

9,10-Dimethyl-1,2-benzanthracene↗

The rat in experimental obstructive hydrocephalus.

The effects of kaolin-induced hydrocephalus on CSF turnover was studied in rats by ventricular perfusion and the results compared to normals. The mean CSF formation rate measured in 20 normal rats was 2.83 microliter/min. Approximately three weeks after intracisternal kaolin, the mean CSF formation rate in 17 hydrocephalic rats was reduced by 40%. CSF absorption in hydrocephalic and normal rats varied linearly with perfusion pressures between -10 and 10 cm H2O. The response of CSF absorption rate to changes in intracranial pressure was decreased in hydrocephalic rats. Ventriculomegaly of hydrocephalic rats was associated with a dilated spinal cord central canal. This suggests that kaolin hydrocephalus alters CSF pathway in rats in a manner similar to that described previously in cats and dogs. Ventriculomegaly is limited by the supporting structures of the brain because the removal of the calvarium and dura after kaolin results in massive ventriculomegaly.

Animals↗

Immunity to transplantable nitrosourea-induced neurogenic tumors. I. Potentiation of tumor immunity with Corynebacterium parvum.

Various injection schedules of C. parvum and tumor cells of the nitrosourea-induced malignant neurinoma, TR-481, were used to induce tumor immunity in syngeneic CDF rats. Although subcutaneous injection of the poorly immunogenic TR-481 cells alone or with C. parvum caused retardation of growth of 2 x 10(5) TR-481 cells injected 1-3 weeks later, no significant difference in tumor size or incidence was obtained, as judged by tumor growth at 8 weeks. In contrast, injection of TR-481 with C. parvum into C. parvum-presensitized rats caused a more significant degree of tumor immunity with complete inhibition of the challenge tumor growth in 17-33% of the animals. Repeated subcutaneous injection of gamma-irradiated TR-481 tumor cells mixed with C. parvum also proved effective, resulting in absence of tumor growth in 40% of the rats. Tumor immunity was specific, since growth of an unrelated tumor was unaffected. It is suggested that local immunological reactivity to C. parvum in the immunizing tumor promotes development of specific tumor immunity.

Adjuvants, Immunologic↗

The effect of cold-induced brain edema on cerebrospinal fluid formation rate.

The net contribution of vasogenic brain edema to cerebrospinal fluid (CSF) formation was studied by ventriculocisternal perfusion. Individual cats were perfused both before and 2 1/2 hours after a severe cold-induced injury to the cerebral cortex, and the results were compared. Although the edema had occupied the larger part of the hemispheric white matter and bordered the lateral ventricle, a decrease rather than an increase in CSF formation rate was observed. This decrease was related to a decrease in the cerebral perfusion pressure by a regression equation that was not affected by the cold injury.

Animals↗

Evidence for the movement of fluid, macromolecules and ions from the brain extracellular space to the CSF.

This report examines the effect of decreasing serum osmolality on movement into the ventricular system of fluid and of test material injected into the brain. Trace quantities of 22NaCl and 125I-labeled cat serum albumin (CSA) were injected into cerebral white matter of cats. The rates of cerebrospinal fluid volume flow, and appearance of 22Na and 125I-CSA were measured in the effluent fluid using ventriculocisternal perfusion before and while serum osmolality was acutely decreased by the intravenous infusion of a 60 mOsm sucrose solution. As compared to the control period, at the end of the infusion serum osmolality decreased from 321 +/- 4.2 mOsm to 283 +/- 4.0 mOsm and CSF volume flow increased from 21.8 +/- 2.3 microliter/min to 54.9 +/- 4.1 microliter/min (means +/- S.E.). The slope of the regression line describing 22Na influx went from 1.04 to 1.79, while for 125I the slope went from 0 to 1.38. These results suggest that a common pathway may exist for the movement, through the brain and into the ventricular system, of water, ions and large molecules.

Animals↗

Kaolin-induced hydrocephalus impairs CSF secretion by the choroid plexus.

CSF volume flow and sodium (Na+)-influx rates in normal and kaolin-induced hydrocephalic cats were measured during ventricular perfusion with anisotonic sucrose solutions. When ventricular fluid osmolality was 120 mOsm, CSF volume flow ceased for both groups of cats. As ventricular fluid osmolality was increased, the CSF volume flow rate of normal cats increased to 70 microliter per minute, and in hydrocephalic cats to 40 microliter per minute. In normal cats, for ventricular fluid osmolality between 50 and 350 mOsm, Na+-influx was constant and thought to occur by diffusion; while for higher osmolalities, Na+-influx increased. In hydrocephalic cats, Na+-influx increased over the entire range of ventricular osmolality but was less than in normal cats. Acetazolamide decreased the CSF volume flow in normal cats by 40 percent, but was ineffective in hydrocephalic cats. These results suggest that CSF secretion by the choroid plexus of cats with kaolin-induced hydrocephalus is impaired.

Animals↗

Sodium exchange between blood, brain, and CSF in normal and hydrocephalic cats.

The exchange of sodium between blood, brain, and cerebrospinal fluid was studied in normal and kaolin-induced hydrocephalic cats. The ventricles were perfused to measure fluid formation and Na+ exchange rates. 22Na was added to the perfusion fluid or injected intravenously as a tracer for Na+ movement. Na+ and 22Na were also measured in cortical gray and white matter. Na+ relative specific activities were calculated for brain, effluent fluid, and serum. With 22Na in the perfusion fluid, Na+ exchange was not different from nascent Na+ influx for both normal and hydrocephalic cats. Na+ relative specific activities of cortical gray and white matter were 10 times greater in hydrocephalic than in normal cats. This difference in Na+ relative specific activity for brain may be due to a higher diffusion constant or to a lower brain capillary permeability. When 22Na was given intravenously, the Na+ diffusional exchange for normal cats was less than that measured when 22Na+ was in the perfusion fluid. In hydrocephalic cats, the Na+ diffusional exchange was effectively zero. Na+ relative specific activities of cortical gray and white matter were the same for normal and hydrocephalic cats. These findings suggest that the impaired Na+ diffusional exchange may be due to pathological changes in the choroid plexus.

Animals↗

The effects of ventricular fluid osmolality on bulk flow of nascent fluid into the cerebral ventricles of cats.

The effects of ventricular fluid osmolality on the bulk flow of nascent fluid into the cerebral ventricles of anesthetized cats was measured during ventriculocisternal perfusion. This nascent fluid consists of both cerebrospinal fluid (CSF) and fluid which results from an osmotic gradient between ventricular fluid and the blood and/or brain. Perfusions were carried out with both mock CSF and with solutions containing either sucrose, urea, or NaCl. Differences between the normal bulk flow rate of nascent CSF and bulk flow rate measured during perfusion with anisotonic solutions were linearly related to corresponding differences in osmolality of the effluent fluid from the ventricles. The coefficients of somotic flow using sucrose (0.231 mul/min per mOsm) and NaCl (0.224) were similar, and greater than that using urea (0.156). During perfusion with sucrose when effluent osmolality increased by 200 mOsm (63% of normal), bulk flow rate of nascent fluid increased by 50 mul/min (200% of normal). Flow was undetectable when the effluent osmolality was 190 mOsm (decrease of 135 mOsm), although osmotically active particles continued to enter the ventricular system. Intravenous injection of acetazolamide reduced these coefficients to similar values of 0.0963 for NaCl, and 0.0955 for urea. In all experimental conditions no changes were found in cerebral water content. These results suggest that the increased bulk flow which occurs during perfusion with hypertonic solutions originates from the choroid plexus.

Acetazolamide↗

The sink action of cerebrospinal fluid volume flow. Effect on brain water content.

Effects of changes in serum osmolarity on volume flow of fluid into the cerebral ventricles of cats were measured by ventriculocisternal perfusion with mock cerebrospinal fluid (CSF), mock CSF containing acetazolamide, or a 30 mOsm/liter sucrose solution. Serum osmolarity was altered by intravenous infusion of a sucrose solution ranging between 10 and 650 mOsm/liter changing volume flow. For all perfusion fluids, regression lines relating volume flow to infused solution osmolarity were parallel. After infusion of a 10 mOsm/liter solution, brain water content increased. One hour after infusion, volume flow returned to normal, although serum was still hypotonic. Gray matter water content was still elevated; white matter returned to normal. The results suggest that the source of increased volume flow is the brain, and that the CSF acts as a sink, limiting excess water accumulation during water intoxication.

Animals↗

An angiographic study of the carotid arterial and jugular venous systems in the cat.

Standard techniques for performing carotid angiography in dogs and in man were adapted to the cat in order to study the vascularization of both intracranial and extracranial structures. Venous drainage was examined by venography of selected vessels. The carotid-cerebral and the vertebral-basilar arterial systems of the cat were studied, although no attempt was made to define the territory supplied by each system. In serial angiograms, vascularization of the rete mirabile conjugatum was visualized and distinct arterial and venous retia were delineated. Large facial veins were seen approximately one second after the intra-arterial injection of radio-contrast material. The early filling of the large facial veins appeared to be the result of an artery-to-venous shunt. Contrast material flowed posteriorly in these veins and drained into the venous rete. When contrast material was injected either into the sagittal sinus or retrograde in the external jugular vein, the internal jugular vein was visible in four of ten cats. This vessel drained blood directly from intracranial contents before anastomosis with the vertebral and external jugular veins.

Animals↗