bluuebunny/crossref_metadata_2025 huggingface dataset:
Levocetirizine and rupatadine in chronic idiopathic urticaria
Authors: Johnson Madhulika , Kwatra Gagandeep , Badyal Dinesh K. , Thomas Emy A.
Published: December 2014

Background

Chronic idiopathic urticaria (CIU) is a common dermatological condition. Its pathogenesis involves mainly histamine and also other mediators, including platelet‐activating factor (PAF) and tumor necrosis factor‐α (TNF‐α). In the absence of an exact etiology, H1‐antihistaminics are the mainstay of treatment. Levocetirizine is widely prescribed for CIU. Rupatadine, a newer antihistaminic, has PAF receptor antagonist activity and has shown anti‐TNF‐α activity in vitro. These additional anti‐inflammatory effects may improve its efficacy.

Objectives

This study was conducted to compare the efficacy and safety of rupatadine and levocetirizine, respectively, in CIU patients.

Methods

A prospective, open, comparative, randomized study was conducted in 100 patients, of whom 50 were treated with levocetirizine and 50 were treated with rupatadine. Efficacy parameters used were urticarial activity score (UAS) and Dermatology Life Quality Index (DLQI) values. Safety was evaluated by monitoring for adverse drug reactions and by using the critical flicker fusion threshold (CFFT) test and a visual analog scale (VAS) at baseline, and at 2, 4, and 6 weeks.

Results

The mean UAS decreased to 0.10 in the levocetirizine group and to 0.38 in the rupatadine group. Patients in the levocetirizine group showed a more significant (P < 0.001) improvement, although symptoms improved in both groups. Significant reductions in mean DLQI scores were observed in both groups, but the decrease was statistically significant in the levocetirizine group (P < 0.05). Somnolence was the most common side effect in both groups. Patients in the levocetirizine group showed more psychomotor impairment based on the CFFT test. Findings on the VAS showed sedative effects in both groups (P < 0.05).

Conclusions

Levocetirizine was found to be more efficacious than rupatadine in CIU patients, but both drugs caused mild sedation.
Inter‐ and intrarater reliability of the Chicago Classification in pediatric high‐resolution esophageal manometry recordings
Authors: Singendonk M. M. J. , Smits M. J. , Heijting I. E. , van Wijk M. P. , Nurko S. , Rosen R. , Weijenborg P. W. , Abu‐Assi R. , Hoekman D. R. , Kuizenga‐Wessel S. , Seiboth G. , Benninga M. A. , Omari T. I. , Kritas S.
Published: December 2014

Background

The Chicago Classification (CC) facilitates interpretation of high‐resolution manometry (HRM) recordings. Application of this adult based algorithm to the pediatric population is unknown. We therefore assessed intra and interrater reliability of software‐based CC diagnosis in a pediatric cohort.

Methods

Thirty pediatric solid state HRM recordings (13M; mean age 12.1 ± 5.1 years) assessing 10 liquid swallows per patient were analyzed twice by 11 raters (six experts, five non‐experts). Software‐placed anatomical landmarks required manual adjustment or removal. Integrated relaxation pressure (IRP4s), distal contractile integral (DCI), contractile front velocity (CFV), distal latency (DL) and break size (BS), and an overall CC diagnosis were software‐generated. In addition, raters provided their subjective CC diagnosis. Reliability was calculated with Cohen's and Fleiss’ kappa (κ) and intraclass correlation coefficient (ICC).

Key Results

Intra‐ and interrater reliability of software‐generated CC diagnosis after manual adjustment of landmarks was substantial (mean κ = 0.69 and 0.77 respectively) and moderate‐substantial for subjective CC diagnosis (mean κ = 0.70 and 0.58 respectively). Reliability of both software‐generated and subjective diagnosis of normal motility was high (κ = 0.81 and κ = 0.79). Intra‐ and interrater reliability were excellent for IRP4s, DCI, and BS. Experts had higher interrater reliability than non‐experts for DL (ICC = 0.65 vs ICC = 0.36 respectively) and the software‐generated diagnosis diffuse esophageal spasm (DES, κ = 0.64 vs κ = 0.30). Among experts, the reliability for the subjective diagnosis of achalasia and esophageal gastric junction outflow obstruction was moderate‐substantial (κ = 0.45–0.82).

Conclusions & Inferences

Inter‐ and intrarater reliability of software‐based CC diagnosis of pediatric HRM recordings was high overall. However, experience was a factor influencing the diagnosis of some motility disorders, particularly DES and achalasia.
THE PRESSURE OF PANCREATIC SECRETION, AND THE MODE OF ABSORPTION OF PANCREATIC JUICE AFTER OBSTRUCTION OF THE MAIN DUCTS OF THE PANCREAS
Authors: Herring P. T. , Simpson Sutherland
Published: December 2014

When the pancreatic duct or ducts are obstructed the pressure of pancreatic secretion rises to a height closely approximating that reached by the bile in obstruction of the common bile‐duct. In the dog and cat the average maximum pressure attained as the result of intravenous injection of duodenal extract is about 300 mm. water. The highest pressure recorded in our experiments was 381 mm. in a dog; the lowest, also in a dog, was 240 mm. In three small Macacus rhesus monkeys the maximum pressure averaged 277 mm. water.

The intravenous injection of duodenal extract brings about a rapid rise of pressure in the pancreas when its secretion is prevented from escaping into the duodenum. The pressure reaches a maximum, and at once begins to fall. Both rise and fall of pancreatic pressure are more rapid than the rise and fall of bile pressure in obstruction of the common bile‐duct.

Carmine gelatine, when injected into the pancreas through its main duct shortly after the death of the animal, tends to rupture the fine ducts, and escapes into the surrounding connective tissue in the manner described by Heidenhain. When injected at a low pressure during life, rupture of ducts may or may not occur. Apart from any escape in this manner, the carmine gelatine passes into the cells of the acini and of the walls of the small ducts, and from them to the exterior. Pancreatic secretion is absorbed at a low pressure, and it is probable that the secreting cells, when the alveolar pressure has reached a certain point, get rid of their secretion by turning it into the lymph stream. The pancreatic juice follows the lymph paths from the pancreas, and finally enters the blood from the thoracic duct. The mechanism of absorption of pancreatic juice is very similar to the mechanism of absorption of bile in obstruction of the bile‐duct.

The expenses of this research have been defrayed by a grant from the Earl of Moray Fund for the Prosecution of Research in the University of Edinburgh.
THE REFRACTORY PHASE ASSOCIATED WITH ONE SINGLE EXCITATORY PROCESS IN YOHIMBINISED NERVE
Authors: Tait John
Published: December 2014

1. In the refractory phase associated with one excitatory process in yohimbinised nerve two distinct stages are present. In the first or absolutely refractory stage conductivity is suspended. In the second relatively refractory stage conductivity, while present, is diminished in amount. Throughout this stage, however, it gradually and progressively increases from zero right up to the extent to which it was present before the excitatory process occurred.

2. Both these stages are present in the recovery of normal nerve after activity.

3. Yohimbine prolongs both the absolutely refractory phase and the relatively refractory phase of nerve. By much the greatest absolute prolongation is in the relatively refractory phase.

4. The total refractory phase of deeply yohimbinised nerve corresponding to one single excitatory process may be as long as 2·2 seconds. The greatest previously recorded prolongation (Trait and Gunn) was ·25 second.

5. Although yohimbine gradually depresses the function of a nerve, and although the immediate effect of activity during yohimbine anaesthesia is to exaggerate this depression of function, yet as regards the repair after activity yohimbine affects merely its rate and not its amount.

The expenses of this research have been defrayed by a grant from the Carnegie Trust. For my supply of yohimbine I am indebted to Drs Hillringhaus and Heilmann, Chemische Fabrik, Güstrow.
STUDIES IN THE REFLEXES OF THE GUINEA‐PIG. I. THE SCRATCH‐REFLEX IN RELATION TO “BROWN‐SÉQUARD'S EPILEPSY.”
Authors: Brown T. Graham
Published: December 2014

1. Of 20 guinea‐pigs 14 have survived the operation of resection of a portion of the right great sciatic nerve for a sufficient length of time, and each one of these has exhibited the movements described by Brown‐Séequard as “epilepsy.” None of these have shown “spontaneous” attacks or the condition of “blepharospasm.”

2. The movements were evoked by stimulation of a special area of the skin, the adequate stimulus being mechanical pressure. Stimuli consisting of loud sounds, the vibrations of which ranged between 32 and 16,000 per second, of a bright beam of light directed into the eye, and of a warm beam of light directed on to various parts of the special area of skin, were inadequate. Electrical stimuli given in the form of galvanic shocks were inadequate, as also possibly they were when given in the form of rapid double faradic shocks.

3. The boundaries of the special zone of skin are larger than those given by Brown‐Séquard. It almost invariably extends further back than the posterior border of the scapula, while it may extend as far forward as the border of the nostril and the edge of the lower lip in the middle line.

4. Changes in the condition of this area, and also in that of the lower limb of the side of the lesion, similar to those described by Brown‐Séquard, were observed.

5. The movements, which consist of tonic contraction of the muscles of the neck and back, and of clonic movements at the hip‐joint, occur in two stages. In the first of these the movements are confined to the side of the lesion, while in the second they spread to the opposite side.

6. The rhythms of the clonic movements observed lay between the limits of 8 and 16 beats per second. The rhythm was slower in the larger animals. It was also slower towards the end of one reflex, and varied when the reflex was evoked from different points in the special area.

7. The clonic movements, as studied in graphic tracings, show a marked resemblance in many of their features to the scratch‐reflex observed in the spinal dog.

8. They differ from this reflex in the overflow to the opposite side, and in the phenomenon of alternation, as well as in the degree of the tonic factor.

9. Once the clonic movements have appeared, they become progressively more extensive up to a certain point as the condition persists. The excitatory value of the maximal stimulus rises.

10. The clonic movements may be inhibited by stimulation of the skin on the abdomen of the opposite side by mechanical pressure. In the early stages this inhibition comes on rapidly, but persists for some time after the cessation of the inhibiting stimulus. In the later stages it is established less rapidly, but lasts a shorter time after the stimulus has stopped. Towards the end of a long reflex response the inhibiting stimulus may only affect the clonic movements by slowing the rate of the beats. When the inhibition of the clonic movements is complete, there is also an inhibition of the tonic contraction of the muscles of the side and hip.
EFFECTS OF HYPOPHYSEAL TRANSPLANTATION FOLLOWING TOTAL HYPOPHYSECTOMY IN THE CANINE
Authors: Crowe S. J. , Cushing Harvey , Homans John
Published: December 2014

The experimental transplantation of fragments of ductless glands has in the past not met with striking success, possibly due to the fact that the principle emphasised by W. S. Halsted, that an existing “physiological deficit” is one of the essentials to a successful “take,” has been disregarded.

Our experiences conform with those of others in showing that the transplanted glandular tissue—in this case the hypopyhsis—is prone to undergo necrosis and in the course of time to become replaced by fibrous tissue. It is nevertheless apparent, particularly in the cases of immediate auto‐transplantation of the gland into the cortex cerebri, that the inevitable early consequence of a total hypophysectomy (cachexia hypophyseopriva) can be postponed; further, in the case of animals in whom a minute fragment only of anterior lobe remains, the transplant seems to have been the means of tiding them over a period in which, according to our previous experiences, death would certainly have occurred. These fragments we have subsequently found to show evidences of the condition which we regard as hypertrophy. The transplants themselves, both anterior and posterior lobe, show histological evidences of retained activity for periods of at least a month.

It has been observed that marked polyuria follows the cortical transplantation of the entire gland; that it disappears after extirpation of the transplant; that it does not follow transplantation of the posterior lobe alone; and, further, that it does not occur in control animals with heterotransplants.
CRUSTACEAN BLOOD COAGULATION AS STUDIED IN THE ARTHROSTRACA
Authors: Tait John
Published: December 2014

1. This communication, histological throughout, is virtually a continuation and extension of a previous publication by W. B. Hardy on crustacean blood corpuscles. The explosive cells discovered by Hardy in the crayfish have been studied in films of isopod blood, and have been found to discharge into the immediately surrounding plasma a material which either itself coagulates or there induces coagulation in the portions of plasma reached by it. In this way a little localised island of coagulation is formed around each exploded corpuscle.

2. These islands, once formed, are fixed structures, with a definite boundary, which has no tendency to become diffuse or to spread outwards. There is thus a limit to the range of action of the explosive corpuscles, and there is no evidence that, as Hardy suggested, they yield a ferment which causes the plasma as a whole to coagulate.

3. On first formation, these localised coagula are plastic structures, which can be modified in shape by movements of the surrounding fluid. They are likewise sticky, and tend to adhere to or entangle any cells with which they come in contact. They soon set and harden, however. In a film that has been kept at rest their usual form is circular.

4. The actual formation of these coagula in situ at a wound may be watched in the amphipod Gammarus, and the part which they play in the natural arrest of hæmorrhage thus studied. They help to stop the bleeding by forming an adherent bunch of globules or botryoidal mass at the site of injury. To these globules issuing blood cells tend to adhere, thus further clogging up the paths by which the blood escapes.

5. The birth of one of these globules is accompanied by a considerable output of kinetic energy, the explosion consisting not merely in a shedding‐out of material from the corpuscle, but in an actual rending and breaking apart of the immediately surrounding clot. This process suggests an analogy with Macdonald's hypothesis regarding the cause of muscle contraction.

6. The part played by these localised coagula must not be taken in the meantime to supersede or dispose of the cell‐agglutination hypothesis put forward by other authors as the cause of the first coagulation in crustacean blood. According to the view here taken, the phenomenon exists alongside of and ultimately associated with cell agglutination as a contributing factor in arrest of hæmorrhage.

7. A second coagulation of isopod blood, this time involving the whole plasma indiscriminately, may be made out in addition to the afore‐mentioned localised coagulation. There is no histological evidence to associate this second coagulation with the disintegration of any one particular element of the blood more than another.

The expenses of this research were defrayed by a grant from the Carnegie Trust.
STUDIES IN THE REFLEXES OF THE GUINEA‐PIG. II.: SCRATCHING MOVEMENTS WHICH OCCUR DURING ETHER ANÆSTHESIA
Authors: Brown T. Graham
Published: December 2014

1. About 63 per cent. of guinea‐pigs subjected to ether narcosis exhibit peculiar scratching movements. These occur in the hind limbs, are accompanied by contraction of certain of the muscles of the back and neck, sides, abdomen, and fore limbs, and resemble the movements which occur in the Brown‐Séquard guinea‐pigs when the specific receiving zone in these animals is stimulated far back.

2. The movements alternate from side to side of the body. With each alternation the animal passes into the mirror posture of that which it has just exhibited.

3. If the movements appear for the first time when the depth of anæsthesia is relatively light, they are relatively great in extent; but if then the depth of anæsthesia is increased, they gradually diminish, till they disappear altogether. If they appear first when the depth of anæsthesia is relatively great, they are relatively small in extent, and increase as the depth of anæsthesia decreases, till they cease suddenly.

4. In many cases the movements seem to occur “spontaneously.” In some cases they seem to be started by a definite peripheral stimulus, and in other cases by asphyxiation.

5. The movement of each hind limb, when analysed, is found to consist of a tonic contraction of certain muscles, during the persistence of which clonic movements may also occur. In some cases these are absent. The clonic movements often appear for the first time after the appearance of the tonic contraction. In such cases they are found to consist of sudden, brief cessations and re‐establishments of the tonic contraction. The clonic movements never occur unless the tonic contraction has appeared. The beats of the clonic movement gradually increase in duration in each series. The average rhythm of the clonic movements is about 7·5 per second.

6. The clonic beats are greater on the side of the lesion in guinea‐pigs in which the Brown‐Séquard phenomenon has been developed as a result of the removal of part of one great sciatic nerve.
A COMPARISON BETWEEN THE PROPERTIES OF PROTAGON AND THE PROPERTIES OF A MIXTURE OF PHOSPHATIDES AND CEREBROSIDES
Authors: Cramer W.
Published: December 2014

If Gamgee and Roscoe have correctly described the properties of protagon, and if Thudichum and Rosenheim and Tebb have correctly described the properties of a mixture of phosphatides and cerebrosides, it is clear that these differ in so many fundamental properties that they cannot be identical, i.e. protagon cannot be a mixture of phosphatides and cerebrosides.

It remains to explain why protagon (as understood by Gamgee) has been erroneously held to be such a mixture.

The explanation is to be found, as Wilson and I pointed out, in the observations of Gies. This author showed that a substance which has all the properties of protagon (as understood by Gamgee), and which could not be separated into phosphatides and cerebrosides by recrystallisation from alcohol and washing with ether, was changed by prolonged treatment with warm alcohol at 40° into a substance which had all the properties of a mixture containing phosphatides and cerebrosides and which could be partially separated into these substances by recrystallisation from alcohol and washing with ether.

This statement agrees with all the facts known about protagon as understood by Gamgee.
STUDIES IN THE REFLEXES OF THE GUINEA‐PIG. III.: THE EFFECT OF REMOVAL OF THE CORTEX OF ONE CEREBRAL HEMISPHERE
Authors: Brown T. Graham
Published: December 2014

1. In certain of the reactions of the hind limb of the normal guinea‐pig to similar stimuli applied to the same points of the skin there is a possibility of two different reactions (flexion and extension).

2. After removal of the cortex of one cerebral hemisphere the reactions of the guinea‐pig to mechanical stimuli applied to symmetrical points differ on the two sides.

3. Where such difference is seen, that on the crossed side is one of extension. The best example of this is the “extension reaction” obtained by a mechanical stimulus applied to the skin of the side of the thorax just behind the caudal border of the scapula.

4. The reaction on the uncrossed side is one of flexion. This is best seen in the “scratch reaction” obtained by stimulating in the same way the corresponding area on the side of the lesion.

5. Both these reactions may persist for at least 66 weeks after the production of the lesion.

6. The presence of these reactions is probably due to raised reflex excitability of the spinal cord—on the one side to an exaltation of flexion reflex excitability, on the other to one of extension reflex excitability. The production of these two opposite reactions by a unilateral cortical lesion may be connected with the normal alternation of movements in the hind limbs of the guinea‐pig as seen in the movements of trotting.

7. That flexion reflex excitability is raised upon the same side of the spinal cord as the lesion is further shewn by the reactions in the “anæsthetic scratch𠄍 when produced in these guinea‐pigs. The movements in this state are similar to those of the scratch‐reflex, and are found to be greater on the side of the lesion. In some cases they are confined to that side.
THE ACTION OF YOHIMBINE ON THE HEART, WITH SPECIAL REFERENCE TO TOXIC HEART‐BLOCK
Authors: Tait John
Published: December 2014

This communication consists of a special and of a general part, of which the latter is the more important. The special part deals with the action of yohimbine on the heart. The general part arises out of the special, and includes a discussion on three of the four cardinal properties of heart tissue recognised by Engelmann, viz. conductivity, irritability, and contractility.

A. Special:—

(1) Yohimbine does not alter the absolutely refractory phase of the heart, or, to be more precise, it does not affect the ratio A/S, where A = duration of absolutely refractory phase and S = time of systole.

(2) In sufficient concentration it greatly prolongs the relatively refractory phase.

(3) It depresses the irritability of the tissue to induced currents and probably to chemical stimulation.

(4) In concentration sufficient to bring the heart to a standstill it has no depressing action on contractility.

(5) Under yohimbinisation the conducting mechanism as distinct from the contracting mechanism of the heart is readily fatigued.

B. General:—

Evidence is adduced in support of the following conclusions:—

(1) Irritability and conductivity in the heart, just as in the case of nerve, are essentially the same property. No change in irritability can occur without a corresponding change in conductivity and vice versa. When Engelmann attempted to separate the two properties he was led astray by a wrong assumption.

(2) It follows from the above that the internal mechanism responsible for the existence of irritability and conductivity is a single thing. We may for convenience call it the excito‐conducting mechanism.

(3) It also follows, provided the distinction initiated by Engelmann between irritability and contractility is upheld, that the heart muscle is capable of excitation only through the excito‐conducting mechanism.

(4) The excito‐conducting mechanism is in more close functional and possibly structural relationship with the contractile mechanism than are the nerve fibres with the contractile mechanism in a skeletal muscle. After activity the cardiac excito‐conducting mechanism undergoes repair at a much slower rate than ordinary nerve fibres.

(5) Toxic heart‐block, which has received different explanations at the hands of different observers, is due to a depressing action on the excitoconducting mechanism. The individual explanations advanced to account for the condition are all aspects of one complex change, each feature of which is present at the same time, while no single one can be present without the others.

The expenses of this research have been defrayed by a grant from the Carnegie Trust. For my supply of yohimbine I am indebted to Drs Hillringhaus and Heilmann, Chemische Fabrik, Güstrow.
THE TEMPERATURE COEFFICIENT OF CYTOLYSIS IN THE CASE OF THE UNFERTILISED EGG OF THE SEA‐URCHIN, STRONGYLOCENTROTUS PURPURATUS
Authors: Moore A. R.
Published: December 2014

The temperature coefficient for the process of cytolysis of sea‐urchin eggs in sea‐water has been found to be about 200 for a difference in temperature of 10° C.

The temperature coefficient for hæmolysis has been calculated from Gros' data, and found to be about 200 for a temperature interval of 10° C.

In conclusion, I wish to express my sincere thanks to Professor Loeb for his criticisms and suggestions.
STUDIES IN THE REFLEXES OF THE GUINEA‐PIG. VI.: ON THE RELATION BETWEEN MAINTAINED CONTRACTION AND RHYTHMIC DISCONTINUOUS INHIBITION
Authors: Brown T. Graham
Published: December 2014

1. Tracings obtained from the isolated quadriceps extensor cruris of the scratching movements which occur during ether anæsthesia in the guinea‐pig shew that there are present in the single muscle the phenomena already described in the case of the movements of the intact hind limb under the same circumstances.

2. In the composition of the scratching movements there are two factors —the factor of maintained contraction and the factor of rhythmically discontinuous inhibition.

3. The maintained contraction is evidenced as flexion. It may be present alone.

4. The factor of rhythmically discontinuous inhibition is evidenced as inhibition of the maintained flexion. When present, it determines the characteristic “clonic beats” of the scratch.

5. That the “beats” are determined by rhythmic inhibition of a maintained flexion is demonstrated by tracings in which the maintained flexion is at first present alone, but is then complicated by the “clonus.” In these cases the “beats” are produced by relaxations and restitutions of the maintained flexion. The level of the plateau of maintained flexion in the tracings is not overshot.

6. The “notched” appearance in some of the tracings of the scratching phases is to be explained by the occasional continuous inhibition of the maintained flexion—in place of the more usual rhythmically discontinuous inhibition.

7. The isolation of the muscles for the purposes of recording depresses the scratch—as Sherrington has already observed in the cat. This depression falls more heavily upon the factor of rhythmically discontinuous inhibition. A small dose of strychnine seems to increase the likelihood that the scratching movements will appear. Even then the “clonus” is rarely present.

8. The extent of the contraction of the quadriceps extensor cruris in the active scratching phases of the phenomenon varies with the state of the depth of narcosis. It diminishes in successive phases with increasing depth of narcosis, and it increases with diminishing depth of narcosis.

9. The extent of the relaxation of the quadriceps extensor cruris also varies under the same circumstances as the variation of the contraction. Complete relaxation of the muscle is not obtained except under the deepest narcosis. There is therefore a certain amount of “residual contraction” of the muscle during the interphases of the phenomenon. This amount of contraction diminishes with increasing depth of narcosis, and increases with decreasing depth of narcosis. It is possibly nearly related to a true tonus in the muscle.
THE DEVELOPMENT OF THE ELASMOBRANCH PITUITARY
Authors: Herring P. T.
Published: December 2014

The early stages of development of the elasmobranch pituitary resemble closely the early stages of development of the mammalian pituitary, with this difference—that there is no invagination of the wall of the cerebral vesicle in the elasmobranch to form an infundibular lobe.

The pituitary of the elasmobranch is developed entirely from Rathke's pouch, i.e. from buccal epithelium.

The general relation of the pituitary to the ventricles of the brain is, in elasmobranchs, similar to that obtaining in the higher orders of vertebrates, but this is accounted for by the development of a paired saccus vasculosus, each of which pours its secretion into a common infundibular canal.

The wall of this so‐called infundibular canal is lined with epithelium similar in character to that lining the saccus vasculosus. Its nervous structure is lost, being replaced by connective tissue and numerous thin‐walled blood‐vessels. There is no invasion of the wall of the canal by epithelial cells, and no hyaline bodies are formed.

The pituitary body of the elasmobranch is a gland, the secretion of which is poured directly into the blood‐vessels. There is no evidence of any direct secretion by the pituitary into the brain ventricles.

I have to thank Mr Richard Muir for the accompanying illustrations. The expenses incurred have been assisted by a grant from the Carnegie Fund for research work.
THE RELATION OF PROTEINS TO CRYSTALLOIDS. III. HÆMOLYSIS BY ALKALI. IV. HÆMOLYSIS BY HYPOTONIC SODIUM CHLORIDE SOLUTIONS. V. HÆMOLYSIS BY RISE OF TEMPERATURE
Authors: Roaf H. E.
Published: December 2014

1. Addition of alkali to sodium chloride causes an increase in the osmotic pressure of a hæmoglobin solution in equilibrium with it.

2. This increase of pressure runs parallel to the hæmolytic action of the alkalies.

3. Therefore hæmolysis by alkalies may be due to an increase in the osmotic pressure of the hæmoglobin contained in the corpuscles.

4. The experiments failed to show that hæmolysis by acid is accompanied by an increase in the osmotic pressure of the hæmoglobin, but such a possibility is discussed.

5. Hæmolysis by dilution is probably the result of a temporary difference of osmotic pressure.

(a) If the corpuscle wall is impermeable to sodium and chlorine, a difference in pressure of over 1000 mm. of mercury exists before hæmolysis occurs.

(b) The osmotic pressure of hæmoglobin does not show an increase corresponding to hæmolysis by dilution.

6. Hæmolysis by rise of temperature may be due to the increase in the osmotic pressure of hæmoglobin.

7. The relation of cells to inorganic substances can be explained without the assumption that the cell membrane will not allow these substances to pass through.
REFLEX INHIBITION OF SKELETAL MUSCLE
Authors: Forbes Alexander
Published: December 2014

1. There appears to be no foundation for the view accepted by some that inhibition results from stimulation of assimilation in excitable tissues.

2. The dynamic features of the crossed extension reflex and its inhibition in the preparation used by Sherrington cannot be explained in full under all conditions in terms of assimilation and dissimilation in the moto‐neurones as discussed by Hering.

3. There are several reasons for believing that the increased response to a given excitatory stimulus following prolonged inhibition and the “rebound contraction” following brief inhibition are essentially different phenomena.

4. Inhibition when opposing excitation in this preparation does not delay fatigue in the excitatory arc.

5. The effect of prolonged inhibition upon subsequent excitation depends on the strength of the inhibitory stimulus. With moderate stimuli it favours subsequent activity, with strong stimuli it depresses it.

Exceptional cases are found, probably always after impairment of ventilation, in which every strength of prolonged inhibition causes subsequent depression of excitatory response.

6. The “critical value” of inhibition at which it neither improves nor impairs subsequent excitatory activity appears to be lowered if the excitatory arc is stimulated during the prolonged inhibition.

7. Prolonged inhibition fatigues some part of the inhibitory reflex arc, and impairs its subsequent response.

8. There is evidence, to be published in detail later, showing that fatigue as demonstrated in both excitatory and inhibitory arcs does not involve the centre as a whole, but only the particular path employed.

9. Possible explanations of “subsequent augmentation” and “subsequent depression” are discussed.
RESEARCHES ON THE PERFUSED HEART: THE EFFECTS OF INORGANIC SALTS
Authors: Burridge W.
Published: December 2014

It is shown that many substances may produce heart block if they be perfused through the heart at a too high pressure.

The salts of potassium may be divided into two groups with reference to their action on the heart of the frog. This division is determined by the presence or absence of a “contraction effect,” when the salts are employed in high concentration. The absence of this “contraction effect” with the one group of salts is shown to be due to their action on some of the calcium salts of cardiac muscle. All the salts temporarily abolish the rhythmical activity of the heart.

The division of the salts into these two groups is in accord with their action on the sartorius muscle.

Potassium salts give rise to two types of contraction in the cardiac muscle of the frog, viz., the “tonic contraction” and the “contraction effect.” The former could be produced by all the salts of potassium examined, and seemed to be in some way associated with the rhythmical contraction process; the latter was the determining factor for dividing the salts into two groups, and could be produced in the non‐beating heart.

There is a seasonal, and also individual, difference in the action of a 0·225 per cent. solution of potassium chloride on the frog's heart. In any heart, and at any season, the seasonal differences found in the fresh heart may be reversed or paralleled by appropriate treatment with calcium or potassium salts. The conclusion is drawn that there are seasonal variations in the balance between the calcium and potassium salts in the heart muscle of the frog. It is possible that temperature may be a factor in bringing about such changes.

There are at least three groups of calcium salts in the cardiac muscle of the frog.

The salts of one of these groups seem only to be displaced by such potassium salts as the oxalate and citrate. The results obtained after such displacement suggest that these salts are normally concerned in bringing about some limitation of the direct action of potassium salts on heart muscle.

The other calcium salts are readily displaced by all potassium salts. Such displacement is followed by derangement of spontaneous contractions and of rhythm, such as to suggest the loss of some form of governing or controlling influence. Since restoration to the normal depends on calcium salts, these would appear to keep the cardiac functions in check in addition to being essential to their initiation. Irregularities of rhythm and contraction may appear independently of each other, and for this reason the calcium salts governing these processes are divided into two separate groups. The calcium salts controlling rhythm also appear to mediate the action of the vagus nerve on the heart.

In conclusion, I wish to express my sincere thanks to Professor Gotch for his valuable criticism and advice.
AGE AS A FACTOR IN THE EFFECTS WHICH FOLLOW THYROIDECTOMY AND THYROPARATHYROIDECTOMY IN THE SHEEP
Authors: Simpson Sutherland
Published: December 2014

1. Removal of the thyroid with the contained internal parathyroids in thirteen adult sheep and sixteen lambs from seven to eight months old, led to practically no ill effects.

2. As the result of a similar operation, three lambs about two months old became typical cretins.

3. The complete operation (thyro‐parathyroidectomy) in four adult sheep was followed by no symptoms during the time (three to four months) they were under observation.

4. The same operation (thyro‐parathyroidectomy) in four young lambs (five to seven weeks) resulted early in acute and fatal tetany.

5. Removal of the two external parathyroids from the three cretins when about one year old was followed by only slight symptoms.

With regard to the effects both of thyroidectomy and of parathyroidectomy in the sheep, age is a very important factor.
ON THE RESISTANCE TO ASPHYXIA OF THE DUCK IN DIVING
Authors: Huxley Frances M.
Published: December 2014

In the duck, the relation between the rate of the heart and that of respiration is very close. With inspiration, as in mammals, there is quickening of the heart‐rate; with expiration, slowing, which becomes marked if this phase be prolonged. Thus slowing or stoppage of breathing, however produced, causes a corresponding slowing of the heart—the length of the pause, not the agency which produces it, being the important factor.

Thus submersion of the duck's head gives rise to slowing of the heart, because it produces apnœa; occlusion of the trachea, on the other hand, causes but little change in respiration, and under its influence slowing of the heart is less marked.

Slowing of the heart and the fact of apnœa aid the duck in resisting asphyxia from submersion, because oxygen is spared by the decreased metabolism of the heart and respiratory muscles, and by the absence of mechanical circulation of the air in the respiratory tract.

One reason why, in the duck, asphyxia in air is more rapid than in water must be that in this case there is little sparing of oxygen in this way.
THE CHEMISTRY OF THE MAMMARY GLAND
Authors: Campbell J. Argyll
Published: December 2014

I. Analyses of mammary gland tissue from lactating bitches and cats show that considerable differences exist between different parts of the same gland, between glands of the same animal, and between glands of different animals of the same species.

II Lactose is only found when the gland contains milk. It is not found in the gland of a pregnant animal. Most of it can be removed by draining the gland, so that the amount present is a measure of the milk content of the gland.

III. Since lactose is not a constituent of the parenchyma cells, it must be formed from some other substance in the process of secretion into the alveoli.

IV. The fat obtained from the gland cannot be taken as an indication of the amount of milk constituents it contains, because fat is found not only in the parenchyma cells in the milk within the alveoli, but also as adipose tissue between the alveoli.

The subject of this research was suggested by Dr Cramer, to whom I have been indebted for advice.

The expenses have been defrayed out of the Earl of Moray Fund, University of Edinburgh.
THE ACTION OF PROTOVERATRINE AND ACONITINE ON THE NEURO‐MUSCULAR APPARATUS OF THE FROG
Authors: MacNaughton Marjory
Published: December 2014

1. The action of protoveratrine upon nerve fibres, when tested by the method of rapid serial stimulation, the muscle response being used as an index of the processes occurring in the nerve, closely resembles that of yohimbine. A protoveratrinised nerve shows “fatigue” upon activity and recovery after rest. A rest of several minutes is sometimes necessary before the conductivity of the nerve is restored, There is no “Wedensky effect.”

2. There are, however, certain differences between protoveratrine and yohimbine. Protoveratrine produces a more lasting “fatigue” in nerve fibres than does yohimbine. Again, the snap reflex in the frog produced by yohimbine is not produced by protoveratrine.

3. The action of aconitine upon nerve fibres is similar to that of protoveratrine.

4. Protoveratrine has a special action upon the myo‐neural junction. After this has been exposed to the action of protoveratrine, stimulation through the nerve causes a rapid and permanent “fatigue.”

5. Aconitine is without this action.
RESEARCHES ON THE PERFUSED HEART—SOME ACTIONS OF ACIDS AND ALKALIS
Authors: Burridge W.
Published: December 2014

Alkalis produce two types of ventricular contraction. The one produced by small concentrations of alkali (Gaskell) depends on the calcium salts in the perfusing medium; the other is not so dependent. It is an alkali rigor.

Acids produce two main types of ventricular contraction. Certain organic acids produce a slow developing rigor contraction which destroys the contractile material.

Certain inorganic acids produce a quickly developing contraction capable of repetition.

Lactic acid produces a contraction of intermediate type.

The perfusion of acids through the heart changes the normal reaction of the ventricular wall to sufficiently concentrated solutions of calcium or potassium salts. The change suggested is that of altering the permeability of some membrane or membranes to these salts.

The physiological neutralisation of an acid is not adequately performed by a bicarbonate but it is by a phosphate.

Under the conditions of these experiments the hydrogen ion adversely influences those functions of the heart subserved by the sarcoplasm and its junction with other contractile elements.

The actions of the hydrogen ion are determined by the displacement of other inorganic elements in the tissues, calcium salts being important elements so displaced.
THE BLOOD‐VOLUME OF COLD‐BLOODED ANIMALS AS DETERMINED BY EXPERIMENTS UPON FROGS AND LIZARDS
Authors: Fry H. K. , Adelaide M. B.
Published: December 2014

1. The blood‐volume of cold‐blooded animals, such as frogs and lizards, is satisfactorily expressed in the formula B= Wn/k, where n has a value of about 1·2 and k is a constant to be ascertained for each species.

2. The blood‐volume is accordingly neither proportional to the body surface as in the warm‐blooded animals, nor to the body weight.

3. It appears, however, as suggested by Dreyer and Ainley Walker (5), to be proportional to the weight of the osteo‐muscular system of these animals.

4. A sexual difference is found between male and female frogs similar in character to the sexual difference shown to exist in warm‐blooded animals (4).

5. In Meeh's formula for body surface (S = kW⅔) the best n for my frogs and lizards is 0·68, giving an average k of 11·2 for frogs and 11·6 for lizards
FURTHER EXPERIMENTS ON THE RELATION BETWEEN THE ACTION OF CALCIUM SALTS AND ALKALIES ON THE PERFUSED HEART
Authors: Burridge W.
Published: December 2014

1. A previous finding of the author that the increased tonus which follows the addition of traces of alkali to a solution perfusing the heart is dependent on the calcium salts in the perfusing solution is confirmed.

2. It is suggested that this action of the alkali is mediated by a change in the state of aggregation of some of the heart colloids.

3. It is shown that the action of the alkali in inducing changes whereby the effective action of a given concentration of calcium in producing tonus is increased, is antagonised by calcium salts.

4. It is suggested that calcium salts induce a state of aggregation in certain heart colloids which is unfavourable to their own activity in producing tonus.

5. It is shown that alkalies first prolong and then shorten the refractory period of the heart, and that a marked summation of contractions is made possible.
ON THE INHIBITORY ACTION OF THE PERIPHERAL NEURONES IN THE HEART OF THE FROG
Authors: Letters T. A.
Published: December 2014

The results recorded show that in the frog a sudden rise of the intraventricular pressure above the normal produced by clamping the aortæ causes a temporary decrease in the rate of the heart if the peripheral neurones of the heart are not interfered with; but that an acceleration is produced when these neurones are thrown out of action by the application of atropine. The observations seem to indicate that these neurones play a part in regulating cardiac action.
THE DEATH TEMPERATURE OF NERVE
Authors: Halliburton W. D.
Published: December 2014

1. The irritability of frog'
s nerves was tested by the application of weak induction shocks, and mechanical excitation to muscle‐nerve preparations.

2. When the temperature of the Ringer'
s solution, in which parts of these nerves are immersed, is raised, the heated portion of the nerve loses both its excitability and conductivity at the same temperature and at the same moment.

3. This temperature is identical with that at which the first protein in the series contained within nerve‐protoplasm enters into the condition of a heat‐coagulum.

4. If the heating takes place fairly rapidly (that is, if the nerve reaches and remains at the desired temperature for a few minutes), the death temperature is 40°–41° C.

5. But more prolonged exposure to temperatures a few degrees below this effects the same result. The lowest temperature used (36·50°C.) accomplishes this end in a little over an hour.

6. This is exactly parallel to what happens when one heats the protein extracted from nervous tissue by saline solution. Opalescence, the initial visible sign of heat‐coagulation, sets in at 36°C., and if the heating is prolonged at this temperature culminates in the production of flocculi.

7. It is also paralleled in experiments on the shortening of nerve under the influence of heat; shortening begins at the temperature of opalescence, and although it is not energetic until 40°C. is reached, full shortening can be obtained at the lower temperature provided sufficient time is allowed.

8. The abolition of nervous irritability produced by such temperatures is like the heat‐coagulation of a protein in being an irreversible phenomenon.

9. Alcock's conclusion that the cause of ilerve‐death at an elevated temperature is due to the coagulation of the first protein is thus fully confirmed.

10. This is strengthened by the consideration that in warm‐blooded animals the death temperature of nerve is higher, and is there again identical with the coagulation temperature of the first of the series of proteins contained in this variety of nerve.

11. Alcock's method was different from the one mainly used in the present research. He employed the galvanometric response as the “sign of life” in the nerves he used, and heated his nerves for periods of 5 minutes.

12. I have, however, in a few experiments used this method also, and find that a temperature as low as 36·5°C. will abolish the electrical sign of life, provided it has been kept up for a little more than an hour.

13. v. Miram's results in which he puts the death temperature of frogs' nerves at 47°C., I am wholly unable to explain.

I am indebted to the Government Grant Committee of the Royal Society for a grant which has enabled me to pay the expenses of this investigation. A few years ago I placed the research in the hands of my former demonstrator, Mr V. W. Draper, B.Sc., but, after a few preliminary experiments which I have incorporated in the present paper, he was obliged to abandon the work owing to ill‐health.
THE PROPRIOCEPTIVE REFLEX OF A FLEXOR MUSCLE
Authors: Asayama Chuai
Published: December 2014

1. Quick stretching of tibialis anticus by a sharp pull on its tendon as the muscle lies slack in the decerebrate or spinal preparation (cat) elicits a reflex contraction of the muscle. The reflex is also obtainable in the intact animal under narcosis. It is more marked in the decerebrate than in the spinal preparation.

2. The reaction is a proprioceptive reflex, the only afferent nerve required being that belonging to the muscle itself. The tendon of the muscle and the muscular part immediately adjacent to the tendon are not essential for the reflex. It is not therefore a tendon phenomenon, strictly speaking. It may be termed a stretch‐reflex.

3. The minimal amount of stretching required to evoke the reaction is very small, a stretch amounting to 1 mm.—that is, less than 1/100th of the total length of the muscle—being sometimes sufficient. A stretch amounting to about 1/13th of the total length of the muscle evoked the reflex in fullest amplitude.

4. Rate of stretching is an important factor in the stimulation, a slow stretching, however ample, being apparently unable to evoke the reflex.

5. The contraction has often the myographic appearance of a simple twitch, lasting about 1 second; but under certain circumstances it is considerably more prolonged. When well marked, it develops force enough to raise a weight of more than 30 grms.

Sometimes the response is multiple, and 2–4 separate twitch‐like contractions succeed each other in quick succession.

6. The latent period of the reflex is shorter than that for reflexes evoked from the muscle by other afferent channels.

7. When the reflex response of the muscle has been tired out for the ordinary “flexion‐reflex,” this proprioceptive stretch‐reflex persists unaffected by that fatigue.

8. Strychnine increases the reflex.