The hypo- and hyperglycemic curves are very similar and are in agreement with the physico-chemical phenomena already explained. Both curves reach their maximum within 35 minutes; more or less, and only differ in the mechanism of their production. For hypoglycemia it is necessary to apply the insulin intravenously, and for hyperglycemia the ingestion of glucose is sufficient, considering in both, such factors as age, weight, general conditions of the subject, etc.
If we lower the blood sugar to less than half its normal quantity, in a thirty five year-old, one hundred-thirty-two pound, non-diabetic individual, we will observe the following: 20 minutes after the intravenous insulin injection, in addition to a slight asthenia, the sensations of hunger and thirst begin almost simultaneously; these sensations are experienced normally when the individual needs energy foods.
The energy food par excellence is glucose. Experimentally we have verified that the lack of glucose in the proportion approximately one tenth of the normal quantity produces those sensations. Therefore, hunger and thirst can be defined as general sensations caused by hypoglycemia, in the proportion approximately of one tenth of the normal quantity.
In addition to these sensations, as a result of the increased reduction of the blood glucose, asthenia is experienced, manifested on many patients by the diminution of visual acuity. We know that glucose is burned, discharging H2O and CO2 and releasing a certain amount of energy. Depending on the organ in which it is produced, heart, nervous system, etc., it could be mechanical, psychological, or neurological, etc. It is understood, according to this, that the asthenia symptom exists when the lack of glucose in physiological quantity reduces energy production.
When hypoglycemia is increased, the glucose or muscular glycogen that the patient had managed to conserve in normal quantity in his tissues also begins to decrease. Manifestations appear revealing the deficit of that element indispensable for tissues. And it will be the most delicate (nervous system, endocrine glands, etc.) which will first manifest their necessity of the energy food par excellence: glucose. When this diminution is approximately 20mg, the following manifestations appear: deep asthenia, light drowsiness, tachycardia and tachypnea (increase of 10 or more beats and 5 or more breaths per minute), general excitation and peripheral vaso-dilatation or vaso-constriction, whether the individual is vago or sympathetico-tonic. These last symptoms appear about 20 minutes after the first. In greater degree of hypoglycemia we observe the following symptoms: sleep, that had already begun, becomes deep; slight and fleeting elevation of temperature, already initiated, reaches around one degree Fahrenheit, appearing almost simultaneously with a very copious and generalized sweating; the blood pressure increases about a half centimeter of mercury (Tycos sphygmomanometer), only for about 3 or 4 minutes, descending to normal at the end of the this period, beginning a state of unconsciousness or hypoglycemic semi-comatose state; certain reflexes, sclerotic pupils, tendinous, etc., beginning to disappear; there is sharp bradycardia and bradypnea (decrease of 10 beats and 4 breaths per minute, approximately).
When glycemia has reached less than half, we observe: profuse sweat, waxen pallor, indifference, deep and calm sleep, loss of some reflexes, mainly those of the eye, bradypnea, bradycardia or, in some patients, tachycardia and tachypnea. (See graph # 1). These symptoms correspond to an intermediate situation between the semi-comatose and comatose state; surely the hunger, the thirst and the asthenia of the beginning have reached a maximum degree, causing autophagy that, along with the other phenomena before mentioned, makes the cellular permeability optimal. (See graph # 3).
According to these symptoms, the glucose deficiency is not only that of the blood, but that all the organs, without exception, and all the cells, are undergoing a cataclysm by the lack of that element. Hypoglycemia has reached sucha level that the blood, to maintain its physico-chemical qualities, takes glucose from the cells of the whole body. (See graph # 3).
Because of the lack of glucose in all the cells, the excess of work done for the purpose of restoring the physico-chemical balance and because of the waste product accumulation, we observed asthenia, sleep, semi-comatose or comatose state, loss of reflexes, etc., that translate to the distress of the central nervous system. It is inferred that if the action has reached a point to give serious manifestations on the central nervous system, surely each and every single tissue of the organism will undergo corresponding effects with greater intensity, each according to its own physiology.
These facts prove that sleep is always produced by the lack of energy food for the nervous cells, glucose being the main or probably the only one. Also, they prove that the waste product accumulation originated by the combustion of the glucose, also contributes to produce it, and when these products increase, it leads to give the appearance of the comatose state (the hypoglycemic coma is similar to other comas, acetonic, uremic, etc.).
If the decrease of the glucose continues, the individual is in a deep comatose state: absolute abolition of all reflexes; appearance of cyanic convulsions; miosis first, later, mydriasis, cardiac asthenia manifested by arrhythmia, decrease of the number and amplitude of the heartbeats; low blood pressure so that the radial pulse is not perceptible; respiratory rate is equal to the Cheyne Stokes; pallor is cadaverous; and the temperature is lower than normal. In such circumstances, if the individual is not attended promptly, he perishes in a few seconds.
We will see further that this state will clear up, as explained, during the regression of the symptoms, in which the unconscious state is first in disappearing; the reflexes return, but diminished in intensity and time of reaction; the sleep is now light; the number of heartbeats and breaths is more frequent, acquiring the qualities corresponding to that frequency. When glycemia is approaching normalcy, we are observing that the pulse and the breathing are stabilizing and becoming normal as when the individual is resting; the temperature returns to normal; the sweating, without disappearing, decreases considerably; the same thing occurs with the hunger and thirst. However, the sleep and the asthenia continue with a certain intensity, during two or more hours, not disappearing completely until after one or two days, during which the individual remains more or less somnolent, although the glycemia is normal, due probably to the slow recovery of the central nervous system.
There are patients in whom the glycemia does not return to the original level, staying a few milligrams lower, but always within the normal limits.
The previous description of hypoglycemia has great variations depending on many factors, but I am only going to enumerate those that clearly influence it. The child and the teenager are more sensitive to the action of insulin; from the age of 1 year to 45, an inverse relation exists, but having very slight variations. That is to say, as the age increases, the sensitivity to the hormone decreases. After age 45, the individual seems noticeably less sensitive to the action of insulin, but this sensitivity is not very apparent, as we will see later.
If insulin is injected in small doses, in such way as to produce the hunger sensation (approximate decrease of one tenth of glucose), the action of the hormone is clearly activating the catabolism of glucids and the anabolism of lipids, in order to constitute its reserves, in the form of glycerides. To this is due, mainly, that the subjects injected with small doses of insulin, gain weight. However, we have observed that if the quantity of insulin increases, in such a way that it accelerates the respiratory and circulatory changes, producing a series of symptoms already mentioned, the consumption of oxygen and the release of carbonic anhydride increase, not giving time for the formation of reserves. Then, besides glucose, those fats and albumin reserves in the tissues are burned. The action of insulin can lead to critical autophagy.
If the quantity of insulin is of such a small dose that there is only a lowering of glycemia consisting by approximately between one tenth and one twentieth of the normal level, or the organism takes better advantage of lipids of double energetic power, the liver, and probably the other organs, store in the form of glycogen the glucose that existed in the blood stream (the insulin has been glycogeno-synthesized in small doses). But if we produce a hypoglycemic shock in such a way that, in addition to the reserves of glucose from all the organs containing it, those of the glycogen stored in the liver and in the other organs are taken, then the insulin performs its characteristic function: glycolytic and glycogenolytic, that is to say, typically catabolic.
Indeed, when it is necessary to produce successive hypoglycemias, the greater the number of hypoglycemias previously produced, the less insulin necessary, since each one of them has been decreasing the glycogen reserves. Observation confirms these facts that patients, during repeated action of insulin, become remarkably thin. This is due to the fact that the glyceride reserves have been consumed little by little by the efficient consumption of the circulating glucose. Apparently, the action of insulin on carbohydrate metabolism makes the glucose-glycogen relationship reversible.
If during the action of the insulin or at the same time that it is injected, sugar is administered to the patient, the observed hypoglycemia is light, and, therefore, the action of the hormone is only glycogeno-synthetic.
The function of adrenaline is not pronounced when the glycogen reserves have been, or are almost exhausted. In many patients to whom we have subjected to the loss of less than half of the blood glucose, the application of adrenaline in different doses has never been able to stop the serious symptoms of the moment, for which we conclude by saying: the adrenaline has not been able to release the necessary glucose in the blood or it has released it so insufficiently that the symptoms have continued.
The blood-glucose regulation function of these two hormones is only obviously manifested when their quantity varies within limits near the norm. When the antagonistic action of adrenaline must compensate the energetic action of insulin, it is necessary to resort to other means, because adrenaline, by itself is insufficient to carry out satisfactorily and according to the necessities of the moment, its antagonistic functions.
Glucose is the only indispensable fuel that all the cells of the organism use easily, and with which they cannot do without for the normal performance of their activities. Insulin is the hormone that maintains the glycemic index within certain limits, compatible with cellular life. In harmony with adrenaline, it maintains the reserves of the organism, not only of carbohydrates, but also of fats and albuminoids.
A third factor, the nervous system, takes part in the regulation. Although, to date, its performance has not been clarified, I believe that this is very evident. Remember that at the beginning of this presentation we remarked that some patients experience an intense fear of the insulin injection; when there is such an emotive state, the quantities of insulin necessary to produce the desired effect are smaller, as well as the time required for it. This demonstrates the action that the general nervous system has, not only in hyperadrenalinemia, but also, in general, on the operation of other hormones.
Indeed, function of the vago-sympathetic tonus is to maintain the vital balance in the whole organism, to regulate the cellular metabolism and the operation of various organs.
Cells live in a medium that we must consider amphotropic. In it the active substances, like insulin, adrenaline, mineral ions, etc., some sympathetico-tropic, and others vago-tropic, are in such proportions that the functional balance of these two systems is assured by three main factors which, working in complete harmony, maintain this balance of the reaction of the medium and the ionic level of plasma.
In the vago-tonic state, tissues are alkaline, and contain little ionized calcium. In sympathetico-tonic state, tissues and blood have an acid reaction, containing more calcium and less potassium. The increase of H+ ions is an effect of more calcium and less potassium. The increase of H+ ions is an effect of calcium by its excitation of the sympathetic nerve. However, the excitation of the vagus nerve producing the OH– ion is an effect of potassium.
Summarizing: the state of excitation of the vagal tone corresponds in general terms to an alteration of the K/Ca relation in favor of potassium, to an increase of the cellular permeability to hydration and glycemia. As we said, there are encephalic centers regulating all these changes. The nervous stimulus is transmitted partly by the way of the sympathetic nerve, the suprarenal capsules, or the islets of Langerhans.
The individual under the action of the pancreatic hormone, in dose sufficient to show all the symptoms of hypoglycemia without arriving at the semi-coma state, experiences during the course of this hypoglycemia sharp variations of pulse and temperature.
When insulin is administered intravenously, the symptoms are more accentuated and their appearance is quicker than using any other route.
The pulse frequency increase begins about 20 minutes after the application, to reach an obvious tachycardia during the full hypoglycemic state. During the coma state there is bradycardia, and if this state continues, arrhythmia and extrasystole are observed; finally, the pulse irregularities results in cardiac failure.
Sometimes these variations are abrupt and pronounced; which can reveal some injuries that in the normal state cannot be detected. Variations of up to 30 beats have been observed.
This tachycardia continues until glycemia is normalized, and after this moment there is bradycardia.
When the medications and glucose, are introduced, the tachycardia disappears within 5 to 15 minutes, leaving the pulse below normal. The monitoring of the pulse during the Therapeutic Moment is essential, because it serves to establish the speed of the introduction of medications and glucose. Slowly introduced, they normalize the pulse until it reaches conditions similar to before the application of this procedure. (See graph # 4).
The drop of temperature is quite obvious, in normal sick persons as much as in pyretics (febrile). In the latter ones this drop has reached up to 6 degrees Fahrenheit, to drop even more later on.
When the recovery of the patient is already total because glycemia is near the norm, in certain disorders, mainly in those producing fever, there is an increase in temperature a few hours after having finished with this therapeutic system. Sometimes this increase reaches 104°F. But properly this increase is not caused directly by hypoglycemia; but certain curative medications (mainly arsenical) are therefore producing this pyrexia. When the medications are not the kind producing fever, the temperature stays low at least 12 hours. In some febrile diseases the first application of Cellular Therapy is sufficient to keep the temperature down.
During acute hypoglycemia, osmotic imbalance causes the cells to yield their crystalloids and perhaps part of other substances contained in their protoplasm; there is therefore, a current from inside the cells towards the outside (see graph # 3). This current is not strong enough to make isotonic the blood that remains hypotonic. Said hypotonia produces abundant sudation, which determines along with diuresis, an increase of the blood tonicity by loss of water, accompanied by heat loss, well evident by the increase temperature of the body.
Blood requires a minimum glycemic concentration, because glucose is the immediate fuel and the material most directly usable for the energy needs of all the cells. Blood has a constant osmotic pressure between O.55° and O.58°. For the accomplishment of the cellular functions, a great constancy is necessary in the osmotic pressure in the cells and the medium in which they live. Also, they are accustomed to a constant and fixed superficial pressure of the liquids that bathe them.
The rupture of the physico-chemical balance between blood and cells accentuates more when the superficial tension decreases by virtue of the temperature increase. Such physico-chemical modifications will work on the cells, making them permeable to all the elements contained in the blood, and favoring the diffusion in cellular protoplasm, even of substances not easily diffusible. Therefore, any substance that the blood stream carries (colloid or crystalloid) tends to pass and passes towards the protoplasm, forced by a sort of whirlwind, with which the broken balance is partly reestablished. (See Graph # 4). Cellular endosmosis, favored by the entrance of medications into the blood stream and by its hypertonicity, is performed at the deepest level. The ions taken by the blood stream, positive and negative, are forced to penetrate the cellular protoplasma by the law of ionic balance; also, the other metabolic phenomena governing cellular life, are necessarily partially reestablished. (See Graph # 4).
As we can see, hypoglycemia, altering all the properties by the suggested mechanism, facilitates the passage of medications from the blood towards cellular protoplasm, a thing that does not normally occur.
Such are the conditions that we have tried to reproduce to obtain a therapeutic effect that does not exist in another form. Without the phenomenon of cellular diffusion, there cannot be integral absorption of medications, nor action on germs when they are in the tissues. On the other hand, there would not be metabolic changes favorable for the cell.
The importance of the appropriate selection of the medications, their doses, and the opportunity of their application that we have called the Therapeutic Moment, must be understood. The conditions in which the cell is found which are referred to as avidity, absorption, assimilation, and its maximum physico-chemical change to carry out its metabolic functions, is at its optimal level, and only small doses of medication will be needed for the therapeutic goals as necessary elements for its normal effect.
See Graph # 4. — Graphically we can represent this action by saying that we have represented the expression of a sponge, its interstices remaining under conditions to receive new elements that are in its proximity.
We must take notice that not only have the cells changed their physico-chemical conditions, but, also the germs. They require constant and stable physico-chemical characteristics for their proliferation, and are going to lodge themselves into those places where the organism offers these properties to them. As such, we have Treponema pallidum, for example, that looks for refuge in the nervous centers, where it finds conditions very favorable, filling the characteristics necessary for its proliferation. It can survive there an indefinite time, since the action of medications cannot take place because there are insurmountable barriers to their delivery.
That protected medium where the germs or virus live has also been modified by the action of insulin and has intensely suffered the effect of the physico-chemical phenomena, and as unavoidable consequence, the germs are in an unfavorable situation that can, surely, determine their death.
Experiments conducted in monkeys, applying only insulin, confirm that the virulence of the Poliovirus decreases greatly during hypoglycemia.
We will remember the difficulty of cultivating germs or viruses when we do not have stable conditions of the medium, given their extreme sensibility. If the physico-chemical media of the germs have been modified, superficial tension, osmotic pressure, isoelectric state, pH, etc., the resistance of said germs is found to be very decreased and in precarious conditions for their life.
After the hypoglycemic state that so seriously threatened their life, cells have the aptitude to restore their balance, which will depend on substances contained in the blood. We are at the most opportune moment to adapt them to a new media of life. This problem is of vital importance. We must solve it in a few seconds, resolution that demands efficiency and rapidity, since otherwise the danger of general cytolysis exists.
It is necessary to give to the cells those substances on which, at those precise moments, their life depends. With it the pH, the superficial tension, the osmotic pressure, the isoelectric point, and all the physico-chemical functions return to their normal state for the protoplasmic cellular molecules to regain their normal ambiance.
At this moment, to be able to alleviate the physiological necessity, and at the same time to deliver specific medications to the cells, is ideal. With this, one of the main problems of the therapy will have been solved. (See Graph # 4).
With these studies resulting from our practice, we have managed to fill all the necessities of the moment. Every passing day, the facts are proving to us that we have been solving problems that were insolvable just a few years ago.
RETURN TO THE PHYSIOLOGICAL STATE BY THE CURATIVE ACTION OF MEDICATIONS AND GLUCOSE
In suitable form, specific medications for each case, arrive at the cells of the organism, and work all at the same time, in minimum quantities and in a synergic manner, in such a way that they are not injurious, since they are filling an induced need.
The complete disappearance of the hypoglycemic symptoms takes place in one or two days, sometimes the same day.
It is necessary to remember that when glycemia has decreased approximately 20%, the heart activates its functions and, consequently, those of the liver; thus the transformation of glycogen into glucose is faster. The same thing occurs with muscles and other organs that contain glycogen. Upon activating the circulation, all the apparatuses of excretion eliminate water, which conserves the blood isotonicity and prevents from being altered, the physico-chemical phenomena in which water intervenes (they are the majority). This process is favored by the action of the sympathetic system, upon which adrenaline acts especially, exciting its operation, or perhaps, the proper pancreatic hormone determining, among other things, a cardiac stimulation. After 6 to 10 minutes, there appear, on the contrary, signs of cardiac asthenia, blood pressure drop, decrease pulse rate, etc. This is due to the lack of glucose, energetic element of the heart; to the intoxication of the cardiac fibers produced by the first moment of hypoglycemia; to the probable exhaustion of the excitatory-motor hormone adrenaline; to the lack of bulbar nervous action, sympathetic, and of the heart’s own ganglia; etc., etc.
We have produced hypoglycemias in two subjects that had advanced lesions of the myocardium with renal complications, without having observed serious phenomena of cardiac asthenia. Summing up, we can affirm that when glycemia decreases to approximately less than half of the norm, there is no imminent danger for the cardiovascular apparatus, provided we are not dealing with individuals having reached senescence. In these cases, and in those having suffered some injury in the cardiovascular apparatus, the decrease of glucose by one third, more or less, is not dangerous. In addition, the simultaneous action of sudation and breathing, as well as the increase of the diuresis, influence greatly in the increase of blood hypertonicity, since by such mechanisms, a great quantity of water is eliminated.
The excitatory action of insulin on the sympathetic, first, and vagus, later, has a great effect on other internal secretions. But even without considering this direct action we must consider the direct hormonal synergy of a hormonal secretion over another one. Besides these relationships, every day greater importance is granted to the close ties between hormones and vitamins. In approximately 5 minutes, glycemia raises to two thirds of the norm. This fact comes to verify that in spite of the so energetic devastation produced by insulin, there are always reserves left. And the blood-glucose regulator apparatus, as well as the other apparatuses and systems, with the purpose of putting an end to the difficult physico-chemical situation created by the pancreatic hormone, enter into over-activity during this short period of time. This should be taken advantage of, to establish, between the cells and the blood flow, the inverse phenomenon observed during the period of increase. This is to say that the blood is hypertonic in relation to the cells, (see graph # 4), due to the presence of glucose and to the loss of water (sudation and diuresis). The superficial blood pressure is, equally, increased. The iso-ionico-saline balance, the blood pH, etc., try to return to their previous equilibrium. (See graph # 4).
Unavoidably and necessarily, a current from the outside to the inside, will have to settle down into the cells, to restore the balance between these and blood. The superficial pressure, decreased during hypoglycemia, begins, at this moment, to return to the previous one. Cellular pH, the isotonic and isoionic balances, will return to their primitive state, taking from the blood the elements necessary for the cells to restore their physico-chemical conditions. (See graph # 4).
Our observation of these phenomena demonstrates that selective permeability does not exist, at least at this moment, but that it is complete and simply a physico-chemical phenomenon. At this time, it is accepted that the same thing occurs in the normal metabolic changes of cells. Actually, the facts demonstrate that during the period of increase of glycemia, the crystalloids contained in the blood pass towards the interior of the cells. This is deduced from the physico-chemical considerations, as well as from the clinical signs, because approximately 30 minutes after the application of medications, some of the symptoms that motivated the treatment begin to disappear. This leads us to think that the therapeutic action begins when glycemia decreases one-third from the norm. This action is proportional to the degree of hypoglycemia, whose limit compatible with life is near 16mg of glucose per 100cc of blood.
In order to not expose the patient to the dangers of a very intense hypoglycemia we can affirm, as a general thesis, that the maximum therapeutic action takes place when glycemia in the blood is below 50% of the norm. This degree of hypoglycemia is not dangerous, since in some patients the increase of glucose is observed spontaneously. In such circumstance, the doctor has sufficient time to institute the appropriate therapy in each case. Nevertheless, this hypoglycemic state can be delicate in other patients, especially during their first hypoglycemia, in which case the cautious doctor will have procured beforehand the appropriate medications.
Bear in mind that, except at the moment of hypoglycemia, the habitual glucose level of the individual always tends to reestablish itself, in spite of the fact that the quantity of insulin required in every exchange to produce the same degree of hypoglycemia, is not always the same. That is to say, to make the glucose decrease to less than 50% in the first exchange, the necessary quantity of insulin is always greater than in the subsequent ones, even though the application is always verified when the individual is in equal conditions of glycemia. So it seems that the organism acquires a much greater sensitivity each time it gets hypoglycemia induced by insulin.
It would be important to investigate if this major facility to produce repeated hypoglycemias is due to a disturbance of the function of storage of glycogen by the organs responsible for it, which would not provide glucose after the insulin injection, or if we are in reality dealing with causes of a different nature.
Hypoglycemia as we have described it, corresponds to individuals of an approximate age of 35 years, and weighing 132lb. When these factors are different, the characteristics of the shock also vary.
MODIFICATIONS OF THE APPEARANCE OF HYPOGLYCEMIA ACCORDING TO THE VARIATIONS OF EACH INDIVIDUAL
AGE. — We have applied insulin to patients 3 months old and up, and have observed, invariably, that the action of the hormone is so much more rapid, the younger the age of the patient, until adulthood. The child and the teenager are those who present more intense reactions to insulin. Up to the age of 35 the manifestations are always proportional to the quantity of insulin injected, varying according to the route of introduction. The manifestation of hypoglycemia produces faster and more obvious effects when injected intravenously.
The reestablishment of normal glycemia is verified in a very short time, because the symptoms disappear the same day of the application. Responding, these individuals feel the therapeutic action with extraordinary rapidity. The age, in which the therapeutic effects are more favorable, varies between the age of twenty and forty years, on average. Insulin reactions are faster in the child, but the appearance of symptoms is variable. While in some, tachycardia appears first; in others it is sweat, sleep, or any revealing symptoms, probably of some injury not discovered before the application of insulin. This latter one is, in general, dangerous in the elderly, for the variability of the manifestation of the symptoms and principally because they do not normalize glycemia with facility and rapidity. When, in these subjects, we have been able to raise the glycemia to near the norm, it drops with abruptness again, for which it is necessary to be properly prepared in order to fight cautiously, the abnormal symptoms that appear, as much in the time of their appearance, as in their diversity. It requires sufficient practice in the application of the procedure, in order to offset any danger.
WEIGHT. — One of the factors of major importance for the dosage is the weight of the individual, which is directly proportional to the quantity of insulin necessary to obtain the change of the properties.
Medicament us poisonings produced by previous treatments, autointoxications of intestinal origin, and others of different cause, make individuals hypersensitive. This verifies that in the intensity of hypoglycemia, in addition to the decrease of glucose in the blood and tissues, intervene the accumulated toxins or the lesions produced by the latter. When we find these factors together or isolated in a subject, the organism will respond hypersensitively.
Normal glycemia and age are secondary factors, except for the 50 year old and over. As far as the time in which the symptoms of hypoglycemia appear, we will say that 10 minutes is the minimum, and the maximum is 50, after the intravenous injection.
As verification of the small dependence that glycemia has on the dosage of insulin, we have taken care of diabetic patients with more than 200mg of glucose in the blood (to whom we have applied insulin), having obtained the reduction of glycemia of less than 50% of the norm, that is to say, that the same quantity of insulin determines, in normal and hyperglycemic subjects, an equal glucose reduction.
When there is time, it is preferable to make all the preparations already established for this treatment. But in case of serious or unfavorable conditions, we proceed immediately, with the fundamental goal to save the life of the patient. We can go back later to cure the paralytic locations of the disease or concomitant complications.
The most usual technique for the cases that do not require urgent or special intervention will be described now.
Ahead of time we will have the intestine emptied, preferably with ingested mechanical lubricants, if this is not possible, then with enemas or suppositories.
The weight and age being written down, and being a FASTING CHILD, the dose of insulin equal to the weight in kilos is injected intramuscularly, this is to say one unit per kilo of weight, in children up to 15kg (33lbs.). In children of more than 15kg (33lbs.), the dose of insulin is 75% of the weight. In the same syringe, add 200,000 Units of crystallized penicillin dissolved in glucose serum at 5% and 200,000mg of dihydrostreptomycin. The penicillin as well as the dihydrostreptomycin is dosed by each 5kg (11lbs.) of weight, 100,000 Units and 100,000mg respectively. In another syringe of 5cc, thiamine hydrochloride 5mg, is added, riboflavin 2mg, pyridoxine hydrochloride 5mg, and Nicotinamide 75mg or what is the same, B complex dissolved in glucose solution, in this same syringe, 25mg of propionate of testosterone. The content of these two last medications does not vary with the weight, age, or sex. The testicular hormone is more indicated in the subacute cases and mainly in the disabled.
The dose of insulin, the pulse, the exact time of the application and all the general conditions that are going to be changed by the application of insulin, will be written down on a special chart.
Normally, 30 minutes after injecting these solutions, asthenia is observed in the patient, somewhat sleepy, thirsty, hungry, or a state different from the one before the application. At this moment, he is administered orally, with a small quantity of water, 15 to 200mg of nicotinic acid. It takes approximately 10 minutes for the effect of this vitamin to appear, to reach its maximum within 15 to 20 minutes, maintaining its action for a few more minutes. Then, in most of the cases, we can clearly observe remarkable red flushing of the face and the patient experiencing irritation on all the uncovered parts, a consequence of the vasodilatation produced by the nicotinic acid. In addition to the more accentuated effects of hypoglycemia produced by the insulin, this is the most favorable moment—we have called it the THERAPEUTIC MOMENT—for the absorption and assimilation of the medications that are going to be applied intravenously.
In the vein, prepared ahead of time, will be injected:
in glucose solution at 50% in a syringe of 20cc.
And in another syringe of the same capacity:
in the same dose as injected intramuscularly,
and in addition iodide piperazine 10mg,
in glucose solution at 50%.
The total content of each 20ccsyringe is between 12 and 15cc.
SOME ABNORMAL RESPONSES TO THIS THERAPEUTIC TECHNIQUE IN CHILDREN
The organism of the child is a true thermometer that always responds to all medications with the same precision and in the same length of time. But some unknown details that modify the responses to the various medications escape our knowledge, and we are going to speak now about these cases.
If the patient begins to experience the presentation of all the hypoglycemic symptoms, before the scheduled time, this reveals to us that the dose of Insulin was more than the required quantity for the desired effect. This will make us increase the dose of glucose serum, either before pricking the vein or during the application of curative medications. For the following application we will use this information to decrease the dose of insulin. Reducing the dose of insulin will also decrease the intensity of the hypoglycemic symptoms and their duration. All current data contrary to those previously noted, will force us to increase the dose of insulin for the next application. One, two, and up to five Units are the range of dose we use for this hormone. In each application, we must write down with great care the time of presentation of these phenomena, and their intensity. Although the cases are rare in which convulsions appear after the insulin, the doctor must be ready, not because it is a dangerous symptom, but rather because convulsions hinder to a greater degree the intravenous application, which is already difficult for these small patients.
Some children also present extreme effects to nicotinic acid ingestion, not only the obvious peripheral vasodilatation, but also sometimes a congestion or edema of the glottis that makes breathing difficult. The opposite, that is to say, the lack or the absence of these phenomena of vasodilatation is more frequent. Careful observation will allow us to modify the dose in each case. In very few children the doctor must abstain from giving nicotinic acid.
When it is not possible to inject in the veins of the superior limbs, the doctor must immediately look for those of the neck that are always obvious to the sight and to the touch. In more than a thousand children injected intravenously, only in two have there appeared accidents similar to lipothymias or a deep hypoglycemic comatose state. In theses cases, immediately changing the order of application of the intravenous medications stopped and alleviated these states. That should not alarm the doctor. Instead of first injecting the antiseptic components or the antiviral, without haste, the syringe containing the salts and vitamins is inserted in the needle, slowly, the piston is depressed, and quickly the child responds without the slightest mishap. Once the contents of this second syringe are completely applied, insert the first, and, with the same precaution, inject it. Once the procedure is completed, the child has totally recovered.
Frequently, when finishing, or during the application of the content of the first syringe, the child takes a yellow-greenish coloration. This color should never be the cause of alarm; it is just the coloration given by the Methylene blue and acridines.
For at least 8 hours after the treatment, the patient must ingest warm or cold sweetened liquids. During this time, fever, muscular pains, vomiting, and a kind of grippal state can appear. This almost always follows constipation previous to the treatment, and disappears with the administration of medication that causes the evacuation of the intestine.
BRIEF PHARMACODYNAMIC STUDY
Applying the first formula intravenously, when the patient is at the maximum change of the blood properties, well known under the name of Cellular Therapy, the pharmacodynamic theory is as follows:
The organism tends to regularize its blood glucose content with the hypertonic solution that constitutes the vehicle of injection, with the particularity that it carries the dissolved antiseptics: Tripaflavina, Methylene blue and Resorcin, which are going to act “in situ” by the automatic mechanism, where the pathogenic germs are. This pulls the patient out from the hypoglycemic state in one or two minutes, and carries the chemotherapeutic agents inside the tissues, where, by ordinary methods, the medications do not penetrate.
Methylene Blue 10mg
The particular study of each one of the components is as follows:
UROTROPIN. — Its properties concerning infections are very well known.
ACRIFLAVINE HYDROCHLORATE or TRIPAFLAVINA. — Chemical name: Mono-chlor-hydrate of the 2.8-diamino-10meto-chloride of acridine. Molecular weight: 296.06. It contains 87.58% of acriflavine base and 12.42% of hydrochloric acid; the total chlorine is 24.30% and nitrogen 14.20%. It is a powerful antiseptic, especially for the Cellular Therapy method. A possible mutual incompatibility with phenol is mentioned, but according to clinical experimentation, there is none with Resorcin. Average dose from 0.1 to 0.5% in solution.
METHYLENE BLUE. — Chloride of methylthionine. — Molecular weight: 373.73. — It contains three water molecules that are a tri-hydrate. — It contains blue of anhydrous methylene 85.56% and 14.44% water; in anhydrous salt are 10.03% of sulfur and 13.15% of nitrogen. — Also it can crystallize with 4 or 5 water molecules. — In agreement with the Merck Index (1940), it is an anti-periodic, weak analgesic, and mild antiseptic. As in the previous case, it varies by the application procedure. — The dose is 1.2mg to 2.5mg.
RESORCIN. — Resorcinol or Metapheno-diol, also called Meta-dihydroxybenzene. — Molecular weight 110.05, its purity is 99.5%. — It is an antiseptic, antipruriginous, healing stimulant, and antipyretic. — Average dose is 1 to 5mg.
The second formula is constituted of salts of calcium, magnesium, and iodides, together with vitamin B complex.
Calcium Bromide 7mg
Calcium Gluconate 20mg
Calcium Formate 10mg
Magnesium Gluconate 10mg
Iodide of Piperazine 10mg
In 50% glucose solution.
Also, in acute cases, testosterone propionate is injected. The regenerative effect is shown to be so efficient to many tissues and it is almost sure that among these it includes the nervous tissues and consequently all the others affected.
In addition to the above-mentioned antiseptics, the rest of the formula has the following substances: calcium bromide and calcium gluconate given in ionic form 12.7mg and 17.9mg and iodide of piperazine 50mg respectively. These salts are used in pharmacy, and are the dihydrate of calcium bromide and the monohydrate of calcium gluconate, which gives us altogether 30.6mg ionic calcium. And so that the proportion of ions stays alkaline earth of the blood, it is necessary that the magnesium in ionic form be one-fourth part with respect to calcium, which is obtained with 143mg of magnesium gluconate, in dihydrate form, that gives 7.6mg as well of ionic magnesium. This maintains, therefore, the proportion of these ions in the human blood; those that are the antitoxic of alkaline ions; sodium and potassium, that could have been altered in their proportion, by the change of the blood properties. But as this relationship is regulated by the hormone Cortin, it is only a matter of having an absolute confidence `in the antitoxic effects of the mentioned alkaline ions. Insulin does not act on sodium and potassium, which maintain the inhibition of the blood protids, maintaining constant viscosity and blood volume.
The sometimes-decisive anti-inflammatory action of iodine salts is a fact of daily observation. Sometimes true tumefactions have been dissolved with these salts. It has not been possible to explain the intimate mechanism of their action on those tissues. We have been taking advantage of this therapeutic effect in Poliomyelitis and because of this, doctors of various countries have proclaimed the beneficial action of iodine salts. In cases of Polio, the one that has worked best in Cellular Therapy has been piperazine iodide. It is an organic salt, with its therapeutic action multiplied by piperazine.
In Poliomyelitis, the observed clinical effects have been to fight pain and suffering effectively, and to avoid the fast sclerosis of all affected tissues. Because of this, as much in the acute cases as in the sequels, it has been used with genuine success.
The previous formulas were the fruit of chemical studies guided by clinical data.
< To continue 14 >