Partial Restitution Research Articles

Partial restitution of lesion-induced deficits in the horizontal vestibulo-ocular reflex performance measured from the bilateral abducens motor output in frogs.

The responses of the bilateral abducens nerves to small table velocity steps in the dark were measured in four groups of animals: One group was intact prior to recording (controls), one group was hemi-labyrinthectomized the day before the recordings (acute HL), the horizontal canal nerve was sectioned the day before the recordings (acute HCN) in another and the last group was hemi-labyrinthectomized between 60 and 90 days prior to recording (chronic HL). In controls (N = 6) the slopes of the change in discharge rate to increasingly larger velocity steps increased maximally with about 200 imp/s per 1 degree/s and decreased maximally with about -60 imp/s per 1 degree/s. This difference is explained by low resting rates and by recruitment of spontaneously inactive vestibular afferent, central vestibular and abducens neurons. Results obtained from acute HL (N = 4) and acute HCN (N = 4) animals were practically identical. In neither case was a spontaneous nystagmic activity pattern observed. Results differed from those obtained in controls due to an asymmetric reduction in responsiveness. Comparison of the slopes of the evoked increases and decreases in discharge rates of abducens nerves to increasingly larger velocity steps with those in controls show that normal abducens responses are predominantly controlled by crossed excitation and by uncrossed inhibition. Disinhibition and disfacilitation play minor roles. In chronic HL animals (N = 6) that had posturally recovered to a similar degree, responses evoked by steps towards the intact side at larger velocity steps were slightly reduced with respect to those in acute HL or HCN animals. Responses evoked by steps towards the lesioned side differed between individuals. They were either similar to those in controls (N = 1), to those in acute animals (N = 2) or lay between these two extremes (N = 3). The improvement in response to velocity steps towards the lesioned side in 4 of 6 animals is explained by an increase in activity released by disinhibition. This inhibition in turn is controlled by horizontal canal-dependent input from the intact side. Plugging of this canal abolished all direction-specific responses in this plane in the dark, suggesting that the partial restitution of function of horizontal reflex performance depends exclusively on signals derived from receptors of this canal.

Gefäßschlinge - Ein Beitrag zum vaskulären Kleinhirnbrückenwinkel-Syndrom

Modern diagnostic methods such as brainstem-evoked response audiometry and CT scanning with positive and negative contrast enhancement represent a major advance in the diagnostic evaluation even of small acoustic neuromas. However difficulties arise in differentiation between tumours and other cerebellopontine angle lesions, as shown by means of a case report. An arterial loop of the anterior inferior cerebellar artery (AICA) between the facial and the eighth cranial nerve was the cause of progredient neural hearing loss, peripheral vestibular dysfunction and hemifacial spasm. Vascular decompression was performed with total relief of spasm and partial restitution of hearing. In differential diagnosis of the pathology of the cerebellopontine angle region and the internal auditory canal the clinical symptoms are important.

The phospholipid requirement for activity of the lactose carrier of Escherichia coli.

The transport activity of the lactose carrier of Escherichia coli has been reconstituted in proteoliposomes composed of different phospholipids. The maximal activity was observed with the natural E. coli lipid as well as mixtures containing phosphatidylethanolamine or phosphatidylserine. Phosphatidylcholine or mixtures of phosphatidylcholine with phosphatidylglycerol, phosphatidic acid, or cardiolipin showed low activity. The lactose carrier reconstituted with amino phospholipids of increasing degrees of methylation (dioleoylphosphatidylethanolamine, dioleoylmonomethylphosphatidylethanolamine, dioleoyldimethylphosphatidylethanolamine, and dioleoylphosphatidylcholine) revealed a progressive decrease in both counterflow and proton motive force-driven lactose uptake activities. Trinitrophenylation of phosphatidylethanolamine in the E. coli proteoliposomes resulted in a marked reduction in lactose carrier activity. Partial restitution of transport activity was obtained by detergent extraction of the carrier from these inactive proteoliposomes and reconstitution of the carrier into proteoliposomes containing normal E. coli lipid. These results suggest that the amino group of the amino phospholipids (e.g. phosphatidylethanolamine and phosphatidylserine) is required for the full function of the lactose carrier from E. coli.

Cerebral endogenous substrate utilization during the recovery period after profound hypoglycemia.

Markedly decreased levels of energy-rich phosphates were seen in cerebral cortex after severe hypoglycemia, followed by their partial restitution during the recovery period. During hypoglycemia the nonglucose endogenous substrates were provided by glycolytic intermediates, by Krebs cycle intermediates, and by related amino acids. Other potential substrates for brain oxidation were provided by the breakdown of phospholipids and fatty acids. After a 20-min period of posthypoglycemic recovery, partial restoration of carbohydrates and amino acids occurred, although the amino acid pool size was still reduced. The alterations in phospholipids and fatty acids persisted, while there was a tendency toward normalization of the free fatty acid content. During the posthypoglycemic recovery, treatment with some specific metabolic modulators (6-aminonicotinamide, hopantenate, uridine, L-acetylcarnitine) suggested the possibility of an alternative cerebral substrate utilization owing to modulation of the cerebral biochemical machinery. Thus, increased carbohydrate utilization by hopantenate was consistent with decreased lipid breakdown, while increased carbohydrate utilization by uridine was concomitant with decreased amino acid degradation. In this way, decreased cerebral carbohydrate utilization by 6-amino-nicotinamide was associated with increased lipid and amino acid breakdown. Furthermore, the increased loss of cerebral phospholipids and phospholipid-bound fatty acids by L-acetylcarnitine occurred in the presence of a large glucose availability and was associated with an extensive reduction of cerebral glycolytic flux.

Voluntary and diurnal variation in height and associated surface contour changes in spinal curves.

Height is not a static state. The ‘standing as tall as possible’ heights of 34 females of medium height aged 18–40 were 7–36 mm greater than when they stood as relaxed as possible. All measurements were made with heels on the floor, knees extended and heels, buttocks, back and occiput against the wall. The cervical curve was always, and the lumbar curve usually, straighter with the taller height. Using the same criteria and standing as tall as possible the height on rising could be up to 18 mm greater than later in the day. The decrease in height occurred mainly in the first four hours. Full restitution occurred with a night's rest and partial restitution after relaxation or lighter work.

Recovery after hypoglycemic brain injury: Action of some biological substances on the cerebral metabolism

In artificially ventilated beagle dogs a severe hypoglycemic condition was induced by insulin injection, while the posthypoglycemic recovery was induced by glucose treatment at the end of a 20-min period of spontaneous electroencephalographic silence. The motor area of the cerebral cortex was analyzed for glycolytic metabolites, related amino acids, energy mediators, fatty acids, phospholipids and free fatty acids. The effects on the posthypoglycemic recovery of a intracarotid infusion with some agents (i.e. uridine, cytidine, DL-carnitine, DL-acetylcarnitine, papaverine) were tested. Severe hypoglycemia induced an extensive derangement of the brain metabolism, with partial restitution during the posthypoglycemic recovery. During this condition, the intracarotid perfusion with some biological pyrimidines (uridine, cytidine) interfered with the glycolytic and amino acid metabolites, inducing a decrease in glucose, pyruvate and lactate contents, and an increase in succinate, alanine and glutamine cerebral concns. The lipid carriers ( DL-carnitine, DL-acetylcarnitine) interfered with the fatty acid degradation inducing a magnification of the decrease in the individual (palmatic acid, oleic acid) and total fatty acids, the vasodilating agent (papaverine) being practically inactive.

Immunohistochemical analysis of formaldehyde-and trypsin- or pepsin-treated material

Immunohistochemical studies of paraffin sections of formaldehyde-fixed material and formaldehyde-fixed cryostat sections treated with trypsin or other enzymes were undertaken. Formaldehyde treatment resulted mostly in partial or total loss of antigenicity, as visualized by fluorescent antibody technique in tissue sections. The digestion of sections with trypsin resulted usually in total or partial restitution of antigenicity, previously altered with formaldehyde. This effect is suggested to consist primarily in breaking formaldehyde-induced intermolecular cross-links. Restitution of antigenicity altered by formaldehyde can also be achieved on using pepsin or other proteolytic enzymes, or by some other technique. When the effect of one enzyme proves insufficient, it can readily be complemented by the action of another enzyme applied subsequently. Mild trypsin treatment preserves well the morphological structure of most tissues.

Sensitivity of G 1 phase of the mitotic cycle to chromosome aberrations induced by daunomycin

Cultured human leukocytes were exposed to three concentrations—0.01, 0.015 and 0.02 μg/ml—of the drug daunomycin during the period 0–24 h before harvesting. In treatments lasting 22 h or more, chromatid and chromosome breaks, dicentrics and exchanges were recovered. Treatments between 22-h and 18-h duration yielded higher frequencies of isochromatid type of aberrations than chromatid type. Aberrations were absent or very rare in cultures treated up to 14 h. It was found that daunomycin does not cause mitotic delay of S or G 2 cells under the experimental conditions. Results indicate that ( 1) the sensitive phase of the cell cycle to daunomycin is G 1 ( 2) the chromatid aberrations and exchanges are the results of partial restitution of isochromatid breaks and illegitimate reunions and ( 3) different individuals react differently to the same concentration of the drug.

MESENTERIC ARTERY OCCLUSION WITH INTESTINAL GANGRENE

To the Editor: We surely do appreciate your sending us Dr. Zuidema's letter for comment to be published in a forthcoming issue of your distinguishedArchives. We agree with Dr. Zuidema's statements. To Shaw and Rutledge (1957) indeed belongs the credit for proposing the second-look. Atwell (1961) and Zuidema (1961) reported about such a second look, but both did not have to resect any bowel. In our paper a patient was demonstrated in whom second-look and resection of large portion of intestine were mandatory, to our knowledge still the first case of its kind. We stress the fact that even in apparently hopeless cases thrombectomy may result in partial restitution; second-look after a brief interval clears the situation. By all means not every thrombectomy must be followed by a second look.

Acute Radiation Injury: Pathophysiological Aspects of the Massive Leakage of Albumin into the Gastrointestinal Tract

Rabbits were irradiated with 250 to 1600 r Co60 gamma rays, and the degradation and distribution of albumin in the ani mals were investigated by means of I131-labeled albumin injected intravenously after irradiation. The half life of the labeled albumin was found to be inversely proportional to the radiation dose, indicating an increased albumin catabolism and leakage through the gastrointestinal wall. The excessive excretion of radioactivity in the rabbit irradiated with 1200 r indicates partial restitution of the re- absorption capacity of the intestine. It is concluded that the epithelium and capillaries of the gastrointestinal tract constitute the most sensitive system in acute radiation injury. (D.L.C.)

Factors determining Tension Development in Skeletal Muscle.

Summary.The mechanical factors determining tension in contraction of the single cross striated muscle fibre are investigated by a continuous registration of stiffness and tension at rest and during contraction. The method applied is in principle the same as that described in the preceding paper and stiffness is determined with a measuring frequency of 100 cycles per sec.Dynamic stiffness varies proportionally with tension at rest and during contraction, the proportionality factor at the contraction maximum being from 30–90 per cent above that of the resting fibre. It depends on the initial length and decreases when the contracted fibre is subjected to higher tensions (yielding).From tension, dynamic stiffness and their mutual interdependence the dynamic shortening ability can be computed, and the influence of stiffness and equilibrium length on tension is investigated under different conditions.At all elongations the maximum in stiffness precedes that of tension. Changes in dynamic equilibrium length contribute relatively less to the initial stage of contraction than to the other phases and its influence on the resulting tension decreases with increasing stretch. At the beginning of contraction dynamic shortening may even attain negative values, this decrease being the more pronounced the higher the strength of stimulation and the degree of stretch.When increasing the strength of direct stimuli, tension, stiffness and dynamic shortening increase, the latter varying more with grading than does static equilibrium length.The contribution of stiffness to the resulting contraction tension increases considerably with falling temperature while that given by dynamic shortening correspondingly decreases.The continuously falling tension during fatigue is accompanied by a gradual decrease in stiffness, while equilibrium length has a lowered but rather constant value in different stages of fatigue. Increase in extra‐tension after partial restitution is due to a higher dynamic shortening, stiffness still being essentially lower than in the fatigued and the non‐fatigued fibre. The falling contraction tension during fatigue is not caused by a decrease in number of active elements but is propably due to gradual changes in equilibrium length occurring in the single minute structural eleients proper.Proportionality between stiffness and tension is lacking in the initial phase of contraction (10–20 ms), and within a period where extra‐tension is slight, often so slight that it is difficult to decide whether tension is present or not, considerable changes occur in fiber stiffness which are inherent in the contraction process itself.On the basis of the molecular model previously described a structural interpretation of mechanical factors determining tension is attempted.Apart from extrinsic tension, stiffness is caused by properties of the molecular links and their modifications, by properties of the chains and by the mutual interaction of different chains. The initial difference in the developing rate of stiffness and tension is due to intrinsic tension caused by the interaction of contracting and shunting resting elements, before mechanical consolidation between the elements is established. This increase in stiffness can be so considerable that it inhibits shortening and causes a negative contribution of equilibrium length to the resulting tension.

THE TREATMENT OF DYSFUNCTIONAL UTERINE BLEEDING WITH TESTOSTERONE PROPIONATE

WITH THE RECENT availability of the chemically pure and highly con′centrated androgens, the medical profession is confronted with the problems of therapeutic indications, margin of safety and optimal dosage.Therapeutic indications and margin of safety of a new therapeutic agent are primarily suggested by the response of animal organs to different quanti′ ties of the product. An analysis of the current literature on the effects of testosterone propionate in female animals permits the following conclusions. A. Short treatment (1 to 10 days) produces indifferent or stimulative changes in the ovary of mature and immature rats, depending largely on the dose employed (1, 2, 3). B. Prolonged treatment (6a to 102 days) produces definite degenerative changes in the rat ovary. This effect is, however, temporary, inasmuch as there is restitution of function and partial restitution of structure in the adult rat within 29 days after withdrawal of treatment (4).

STUDIES IN THE PHYSIOLOGY OF THE NERVOUS SYSTEM. XIV.: IMMEDIATE AND SUCCESSIVE EFFECTS OF COMPOUND STIMULATION IN SPINAL PREPARATIONS

1. In the present paper the immediate and successive effects of the compounding of stimuli have been examined in spinal preparations (low spinal and decapitate) as well in the de‐afferented condition as in the normal.2. During double stimulation (immediate effects) there is usually an algebraic summation of the “pure” reactions. This is such—as Sherrington has already pointed out—that the stronger the ipsilateral stimulus relatively is, the greater is the effect of extensor relaxation and flexor contraction during double stimulation; and the stronger the contralateral stimulus is, the greater is the effect of flexor relaxation and extensor contraction.3. When the time relations of the antagonised stimuli are changed, it is found upon the whole that the extension effect during double stimulation is greater the later a contralateral stimulus falls in the period of ipsilateral stimulation; and that the greater is the flexion effect the later an ipsilateral stimulus falls in the period of contralateral stimulation. But often the flexion effect is much greater when the two stimuli are commenced synchronously than when the ipsilateral is commenced a short time after the contralateral.4. Very rarely a slight augmentation of flexor contraction is seen at the commencement of the period of double stimulation when a contralateral stimulus is compounded against a background of weak flexion.5. Less rarely an actual augmentation of extensor contraction occurs during double stimulation, so that this is greater than in the “pure” extension‐reflex.6. This effect is, within limits, proportional to the relative preponderance of the strength of the contralateral stimulus. But if this be changed by weakening the strength of the ipsilateral stimulus, it is found that there exists an optimum relation of the strengths of the two stimuli, and that a further decrease of the strength of the ipsilateral stimulus is accompanied by a reduction of the augmented extensor contraction.7. It is also found that, within limits, this extensor augmentation of contraction during double stimulation is greater the later the contralateral stimulus falls in the period of the ipsilateral. But here too an optimum interval of time between the commencement of the ipsilateral stimulus and that of the interrupting contralateral exists. If the contralateral stimulus be applied at a greater interval of time, the extensor augmentation is decreased.8. Even where the “pure” contralateral reaction evokes abnormal flexion there may be flexor depression during double stimulation. This is seen where the strength of the ipsilateral stimulus is comparatively great. Where the two antagonistic stimuli are small, or subliminal, there may be flexor augmentation of contraction.9. The successive effects of the compounding of stimuli, as seen after withdrawal of one of the stimuli in the phase of double stimulation, seem chiefly to consist in flexion depression and extension augmentation.10. This is seen in the tendency for only a partial restitution of flexor contraction to occur when the ipsilateral stimulus is prolonged after the period of double stimulation. Sometimes no restitution of flexor contraction may occur. When it does occur, it seems to be greater the relatively greater is the strength of the ipsilateral stimulus.11. It is also seen in the tendency for extensor augmentation to occur when the contralateral stimulus is prolonged after the period of double stimulation. This is less the relatively stronger the ipsilateral stimulus is.12. These points mentioned in this summary are some of the chief ones described in this paper, but it is impossible to summarise briefly all the various observations contained in it.

THE CONSERVATIVE SURGERY OF THE TUBES AND OVARIES.

It is twenty years since Schroder first advocated the preservation of the remnant of normal ovarian substance in excision of small cysts of the ovary. August Martin, about the same time, reported a number of cases in which normal portions of the tube and ovary were preserved and the degenerated portion removed. W. M. Polk a year or two later presented the same subject to the American profession and submitted his brilliant results in the conservation of these structures. Since that time contributions have been made to this field of work by Dudley, Kelley, Morris and others, showing definite results in relieving pain, establishing normal menstrual function, and, in a number of instances, being rewarded by seeing the patient bear children. There could be slight excuse for calling attention at this late day to the many ingenious procedures for the partial restitution and preservation of these structures so vital to