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PRINCIPLES OF FIRST AID
IN HEALTH CARE
First aid
 First aid is defined as the immediate care
given to an acutely injured or ill person. It can
literally be life-saving so it behooves all of us
to know some basic principles.What follows
are some rules that cover common conditions
and general practices:

 Don't panic. Panic clouds thinking and causes
mistakes.
First, do no harm.This doesn't mean do nothing. It means
make sure that if you're going to do something
you're confident it won't make matters worse. If you're not
sure about the risk of harm of a particular intervention, don't
do it. So don't move a trauma victim, especially
an unconscious one, unless not moving them puts them at
great risk (and by the way, cars rarely explode). Don't remove
an embedded object (like a knife or nail) as you may
precipitate more harm (e.g., increased bleeding). And if
there's nothing you can think to do yourself, you can always
call for help.
 CPR can be life-sustaining. But most people do it
wrong. First, studies suggest no survival advantage
when bystanders deliver breaths to victims compared
to when they only do chest compressions. Second,
most people don't compress deeply enough or
perform compressions quickly enough.You really need
to indent the chest and should aim for 100
compressions per minute.That's more than 1
compression per second. CPR doesn't
reverse ventricular fibrillation, the most common
cause of unconsciousness in a patient suffering from a
heart attack. Either electricity (meaning defibrillation)
or medication is required.
 Time counts.The technology we now have to treat two of
the most common and devastating medical problems in
America, heart attacks and strokes, has evolved to an
amazing degree, but patients often do poorly because
they don't gain access to that technology in time.The risk
of dying from a heart attack, for example, is greatest in
the first 30 minutes after symptoms begin. By the time
most people even admit to themselves the chest pain
they're feeling could be related to their heart, they've
usually passed that critical juncture. If you or someone you
know has risk factors for heart disease and starts
experiencing chest pain, resist the urge to write it off. Get
to the nearest emergency room as quickly as you can. If
someone develops focal weakness of their face, legs, or
arms, or difficulty with speech or smiling, they may be
having a stroke, which represents a true emergency.
Current protocols for treatment depend on the length of
time symptoms have been present.The shorter that time,
the more likely the best therapies can be applied.
 Don't use hydrogen peroxide on cuts or open wounds. It's
more irritating to tissue than it is helpful. Soap and water and
some kind of bandage are best.
 When someone passes out but continues breathing and has a
good pulse, the two most useful pieces of information to help
doctors figure out what happened are: 1) the pulse rate, and 2)
the length of time it takes for consciousness to return.
 High blood pressure is rarely acutely dangerous. First, high
blood pressure is a normal and appropriate response to
exercise, stress, fear, and pain. Many patients I follow for high
blood pressure begin panicking when their readings start to
come in higher. But the damage high blood pressure does to
the human body takes place over years to decades.There is
such a thing as a hypertensive emergency, when the blood
pressure is higher than around 200/120, but it's quite rare to
see readings that high, and even then, in the absence of
symptoms (headache, visual disturbances, nausea, confusion)
it's considered a hypertensive urgency, meaning you have 24
hours to get the pressure down before you get into trouble.
 If a person can talk or cough, their airway is open.
Meaning they're not choking. Don't Heimlich someone
who says to you, "I'm choking."
 Most seizures are not emergencies. The greatest danger
posed to someone having a seizure is injury from
unrestrained forceful muscular contractions. Don't
attempt to move a seizing person's tongue. Don't worry—
they won't swallow it. Move any objects on which they
may hurt themselves away from the area (including
glasses from their head) and time the seizure. A true
seizure is often followed by a period of confusion called
"post-ictal confusion."Your reassurance during this period
that they're okay is the appropriate therapy.
 Drowning doesn't look like what you think it does. For
one thing, drowning people are physiologically incapable
of crying out for help. In fact, someone actually drowning
is usually barely moving at all (I strongly encourage
everyone to click on this link to learn more about how to
recognize what drowning does look like).
antitoxic serum and its rules for
uses
 ANTITOXINSAn antitoxin is an antibody formed in an animal through the
stimulation of a specific toxin.The usual method of producing an antitoxin is
by the repeated injections of increasing amounts of toxine into a susceptible
animal.The strongest antitoxins are obtained from animals that are very
susceptible to the toxine, but all susceptible animals by no means produce
antitoxins, although repeatedly injected with the appropriate poison.Thus, a
guinea-pig which is very susceptible to diphtheria will not form diphtheria
antitoxin, even after the repeated administration of diphtheria toxine.
Guinea-pigs are also exceedingly susceptible to tetanus and react
characteristically and violently to tet anus toxine, but the repeated injections
of subminimal lethal doses of tetanus toxine into a guinea-pig do not
immunize that animal, nor do they induce the formation of antitoxin. In fact,
Knorr and also Behring and Kitashima have shown that guinea-pigs develop
an increasing sensi tiveness to repeated injections of tetanus toxine instead of
an increasing resistance. In other words, the guinea-pig, a susceptible animal,
lacks the mechanism of antitoxin formation which is possessed in such a high
degree by horses and other animals.Antitoxin produced by the horse or other
animal when injected into the guinea-pig will protect it.
 There are several reasons for selecting the horse for the
production of immune sera for human use. On account of
its size it furnishes large quantities of blood; the serum of
the horse is the blandest blood serum of any known
species; finally, the horse furnishes antitoxin in higher
potency than any other known animal.
Just how and by what cells antitoxins are formed in the body is not
known.They are not formed directly from the toxines. In some ' way
the toxine excites the cell to the formation of the antibody.The
antibody leaves the cell and becomes "dissolved" in the blood and
tissue juices. Perhaps the white blood cells (Metchnikoff), perhaps
the con nective tissue cells (Ehrlich), are chiefly concerned.Within
the body most of the antitoxin is found in the blood, but it also exists
in greater or less concentration in practically all the fluids of the
body and may also appear in the excretions, as the urine, saliva,
milk, and bile.
 Nothing definite can be stated concerning the chemical nature of antitoxins.
Evidence strongly points to the fact that they belong to the higher proteins. In
all probability antitoxins are globulins, at least they come down with the
pseudo-globulin fraction from which they have not been separated.
 Antitoxins are somewhat more stable than the toxines. Further, the toxines
have a more complex constitution than the antitoxins.When the toxines
deteriorate they change qualitatively as well as quantitatively.The antitoxins
have a simpler constitution and deteriorate simply by a loss of power.
 Antitoxins are destroyed by heat, acids, and many chemicals.They gradually
deteriorate spontaneously when in solution.Thus, Anderson has found that
the average yearly loss of the potency of diphtheria anti toxin at room
temperature is about 20 per cent.; at 15° C. it loses about 10 per cent.; and at
5° C. about 6 per cent.There is little difference between the keeping qualities
of untreated sera and concentrated sera. Dried diphtheria antitoxin kept in
the dark at 5° C. retains its potency practically unimpaired for at least years.
Antitoxic sera should always be kept in a cool, dark place.While antitoxin
loses some of its potency with time, and while recently tested sera of known
unit value are always desirable, there is absolutely no reason why a serum,
however old, should not be employed provided a fresh supply is not at hand.
It should be remembered that antitoxins deteriorate quantitatively only ; in
other words, an old antitoxin is quite as useful in proportion to its unit
strength as a fresh serum; in fact, antitoxic sera are frequently two years old
when placed upon the market by manufacturers.
 Antitoxins are strictly specific; that is, they neutralize the corre sponding toxine and have no other
apparent action within the body.The occasional ill effects, such as the serum sickness, following the
injec tion of antitoxic sera, are due to other substances (the proteins in the serum) and not to the
antitoxins themselves. Tulloch 24 on the basis of agglutination tests has separated tetanus cultures
into four types., For tunately, any one of the four antitoxins will neutralize any or all of the four toxins.
It is, however, advisable to prepare the antitoxin with the four different types.
 Antitoxins may be injected subcutaneously, intravenously, into the subarachnoid space, into muscle,
into the brain substance, or into any of the body cavities. Antitoxins are practically useless when given
by the mouth, as very little is absorbed. Antitoxins when injected into an organism disappear rather
quickly. Some of the antitoxin is bound to the corresponding toxine, if any is present, some combines
with the cells, but the greater part is eliminated as antitoxin in the urine, bile, saliva, etc.The antitoxin
produced actively by the body as a result of an attack of disease, or stimulated by the injection of
toxine, is formed continuously and confers an immunity for an indefinite period. Passive or antitoxic
immunity is, on the other hand, transient; it cannot be de pended upon for more than ten days or two
weeks.
 Some persons have sufficient native antitoxin in their blood to pro tect them against diphtheria.This
has been demonstrated through the Schick reaction (see page 201). In such cases the antitoxin is pro
duced naturally for long periods, often during the life-time of the in dividual.
 When antitoxic serum is injected subcutaneously the antitoxin is absorbed slowly. It requires about 48
hours under these circumstances for the antitoxin to appear in the blood in maximum amount.There
fore, when very prompt action is desired, the antitoxic serum may be introduced directly into the
circulation by intravenous injection.
 There are a number of antibodies that are either true antitoxins or closely resemble these antibodies.
Some of these antibodies neutralize the true bacterial toxines, others the poisons of animal origin,
others the poisons of plant origin, and others neutralize the activity of fer ments. The principal
antitoxins, according to this classification, are brought together as follows: (1) Bacterial Antilosins. The
three principal and most potent bac terial antitoxins are those of diphtheria, tetanus, and botulinus.
The following are also considered to have antitoxic properties: pyocyaneus. symptomatic anthrax,
antileukocidin and antilysin against bacterial hemolysins.
 (2) Animal Antitoxins.These antitoxins are
produced by animal poisons belonging to the
venoms.True antibodies are obtained against
snake venom and similar poisons in spiders, eels,
wasps, scorpions, fish, salamanders, and toads.
 (3) Plant Antitoxins.These are antiricin, antiabrin,
antirobin, and anticrotin.
 (4) Ferment Antitoxins. Antibodies may be
obtained against fer ments, such as pepsin, urease,
rosinase, steapsin, trypsin, fibrin ferment, lactase,
cyranase; and antibodies may also be obtained
against the en zymes found in bacterial cultures.
 There are comparatively few antitoxic sera of practical use in
human therapy, just as there are relatively few true bacterial
toxines.The best known antitoxins are those of diphtheria, tetanus,
and botulinus. Numerous other antitoxic sera are found upon the
market or have been described, but they are of doubtful value.
 Antitoxins are valuable both as curative and immunizing agents.
Their preventive action depends upon the fact that they meet the
toxin. unite with and neutralize it, thus rendering it harmless.As
already stated, the antitoxins remain in the body a brief time and
their immuniz ing power, while of a high grade, is transitory.They
disappear in about ten days or two weeks; the immunity must,
therefore, be renewed in special cases by repeated injections of the
antitoxin until the danger is passed.This phase of the subject is
considered in more detail under the prevention of diphtheria and
tetanus.The usual immunizing dose for diphtheria is 1,000 units,
for tetanus 1,500 units.
 As a curative agent antitoxin must be administered early and in sufficient
amount to insure success. It is most important to give the antitoxin early—
before the damage is done.Too great emphasis cannot he laid upon this
point. After the toxin has united with the cells it cannot be dislodged by the
antitoxin.The importance of giving anti toxin early is well illustrated in the
case of diphtheria.When moder ate amounts (3,000 to 10,000 units) are
injected on the first day of the disease the mortality is practically nil.The
mortality increases with each hour's delay.
 The importance of giving this sovereign remedy early is also illus trated in the
experiments of Rosenau and Anderson 25 upon the influ ence of antitoxin
upon postdiphtheritic paralysis. It was found that one unit of antitoxin, given
not less than 24 hours after a fatal dose of diphtheria toxine in a guinea-pig,
greatly modified the postdiph theritic paralysis and saved the life of the
animal, whereas 4,000 units riven 48 hours after the infection did not modify
the paralysis or save the life of the animal. Four thousand units of antitoxin is
an enor mous amount for a guinea-pig weighing about one-half pound.
Weight for weight, it corresponds to 400,000 units for a 50-pound child.The
fact that one unit of antitoxin saves life when administered timely; whereas
enormous doses fail totally when delayed, should be sufficient to place
physicians on their guard ; increased dosage cannot atone for delay.When
cases are seen late in the progress of the disease it is good practice to give the
serum intravenously, so as to neutralize the toxin at once and prevent further
damage. If given subcutaneously, further delay results on account of the time
necessary for absorption.Tetanus antitoxin is a very valuable immunizing
agent, but is of less value after symptoms have appeared, for then most of the
damage has been done.
 Preparation of Antitoxin.The antitoxin used in human therapy is
practically always contained in the blood serum or blood plasma of the
horse.The blood is drawn from the jugular vein into sterile bottles.The
bleeding should never be done until a week or more has elapsed after the
last injection of toxine, so as to allow time for the disappearance of the
poison from the circulation.The horses are given no food for about 24
hours preceding the bleeding, so that the blood may not contain the fresh
products of digestion and metabolism.After the blood is drawn it may be
allowed to clot spontaneously. In the case of horse blood this takes place
more quickly at room temperature than in the ice cheat.
 The clot is allowed to contract for a few days and the serum containing
the antitoxin is then drawn off with a pipet or simply decanted. In this
way a.clear transparent serum is obtained which, if protected against
contamination by the usual bacteriological precautions, is sterile and may
be preserved indefinitely. It is almost a universal practice, however, to add
a preservative; either chloroform (0.3 per cent.), phenol (0.5 per cent.), or
cresol (0.4 per cent.).These preservatives in the amounts named are
harmless when injected and have practically no effect upon the antitoxin
itself.They gradually precipitate the albuminous matter from the serum,
which settles as a white amorphous deposit and which may be
disregarded, as it is harmless.Chloroform produces a better looking
serum, but the less volatile preservatives are usually preferred on account
of their stability and, hence, greater reliability.
 By the method of allowing the blood to coagulate, as above described,
only about one-third of its volume is recovered as antitoxic serum. A
much greater yield ,may be obtained by citrating the blood.: sodium
citrate prevents the clotting of blood. A solution of this salt is placed in
the bottle which is to receive the blood directly from the horse, in
sufficient amount to be present in 1 per cent. of the whole blood.The
corpuscles soon settle to the bottom, leaving the clear supernatant
plasma, which is then decanted or drawn off with a pipet. In this way the
yield of antitoxic fluid is about 90 per cent. of the volume of the blood,
and is. therefore, preferred to the less economical method of allowing the
blood to clot.
 The citrated plasma may further be "purified" or concentrated by various
methods, that generally used being a modification of Gibson's " method,
based upon the earlier experiments of Atchinson.
 Ordinary antitoxic serum contains serum globulins (antitoxic), serum
globulins (non-antitoxic), serum albumins (non-antitoxic), serum nu
cleoproteids (non-antitoxic), cholesterin, lecithin, traces of bile color ing
matter, traces of bile salts and acids, traces of inorganic blood salts, and
other non-proteid compounds. Refined serum contains serum globulins
(antitoxic), traces of serum globulins (non-antitoxic) dissolved in dilute
saline solution.
 Method of Concentrating DiphtheriaAntitoxin.The Banzhaf modification of the original Gibson
method for concentrating antitoxic serums is based on the fact that the antitoxin is contained in
the pseudo globulin fraction of the serum, and has as its purpose the isolation of the antitoxic
pseudoglobulin from the non-antitoxic euglobulin, albumin and other serum constituents.
Plasma, instead of serum, is used for reasons of convenience and economy. By adding
ammonium sulphate to the diluted plasma up to about 30 per cent. saturation and heating the
mixture to 60° C., the euglobulin and converted non-antitoxic pseudo globulin are precipitated,
and removed by filtration. By raising the saturation of the filtrate to about 50 per cent. with
ammonium sul phate, the antitoxin is precipitated.This is collected on filters, pressed, and
dialyzed in parchment bags until all the antitoxin is in solution and free from ammonium
sulphate. It is then neutralized and brought to isotonicity with the blood by sodium chlorid, and
a preservative added. It is filtered first through pulp and finally through a Berkefela filter.
 This method entails a loss of about 25 per cent. of the antitoxic units, but results in a five- or six-
fold concentration of the antitoxin.The process of concentration makes it possible to utilize
serum of low potency; it enables one to give large doses of antitoxin in small volume; and
eliminates the bulk of serum proteins responsible for reactions and for serum sickness.
 Mode ofAction.The mode of action of antitoxins is now fairly well understood. One thing is
certain, and that is that the antitoxin unites directly with the toxin.This may be readily
demonstrated by adding a little antitoxin to some toxin in a test tube and then injecting the
mixture into a susceptible animal; no symptoms result. Diphtheria antitoxin combines with
diphtheria toxin more quickly than tetanus an titoxin combines with its toxin.Thus, in the case
of diphtheria the union between the toxin and its antibody is complete in less than twenty
minutes at room temperature, while in the case of tetanus it requires one hour.These facts are
of practical importance in the work of standardization, in which case the toxines and antitoxins
are mixed in the test tube and the combining action must be complete before the mixtures are
injected into the test animals in order to insure accurate results.
 Ehrlich believes and strongly defends his assumption that an anti toxin unites
with a toxin just as an acid unites with an alkali, that is, the one has a strong
chemical affinity for the other, and the union is simple and direct.The reaction is
complicated only on account of the complex nature of toxine. According to
Ehrlich, there are two primary metabolic poisons in a filtrate of a culture of B.
diphtheriae: (1) toxin, a poison which produces a local destruction of tissue and
acute death; and (2) lozon, a nerve poison that produces late paralysis.There is
also a modified toxin, known as toxoid.Toxin is more actively poison ous and also
has a greater affinity for antitoxin than toxon, which it is able to displace from its
combination with antitoxin.This explains in part the discrepancy between the IA,
and the doses. Ehrlich believed that the union of filtrate with antitoxin seems to
occur in multiple pro portions resembling valancies.
 On the other hand, Arrhenius and Madsen insist that, instead of considering the
toxine as a complex mixture of various substances, such as a toxin, toxon, etc., it
would be simpler to consider it as a single (at least homogeneous) substance
which has a very weak affinity for the antitoxin and that in mixtures containing
toxin and antitoxin there are always both free toxin and free antitoxin. Arrhenius
draws his analogy from known facts in physical chemistry, particularly from
studies upon the relation between solutions of boracic acid and ammonia.These
two substances have a comparatively weak affinity for each other, and in mixtures
all the boracic acid does not combine with all the am monia, but there are always
present both free ammonia and free boracic acid.
 When ammonia and boracic acid are brought together in watery
solu tion some of the ammonia at once unites with some of the
boracic acid to form ammonium borate.This reaction starts with a
certain velocity, but as the mass of ammonium borate increases
the velocity of the reaction gradually diminishes.After a time a
condition is reached when the ammonium borate has a maximum
value and does not further increase, no matter how long the
reaction is allowed to proceed under the given conditions.
 When this condition of equilibrium is reached the mass contains a
certain quantity of water, ammonia, boracic acid, and ammonium
borate; but these substances are not at rest.The ammonia and
boracic acid will always react when in the presence of each other,
whether or not am monium borate is present. But, as the
appropriate amount of ammonium borate remains constant, it is
understood while this continuous association between the
ammonia and the boracic acid is going on there is at the same time
a reversible action—that is, a dissociation of the ammonium borate
to re-form ammonia and boracic acid.These two reactions take
place simultaneously.
 Arrhenius believes that the diphtheria poison changes slowly accord
ing to the laws of monomolecular reactions, that the toxin combines
feebly with the antitoxin, the equilibrium constant being equal for
both.The claim, however, that the toxin is a simple substance having a
weak affinity for the antitoxin and that the combination of toxin and
antitoxin follows the Guldberg-Waage law, and that the reaction is,
therefore, reversible, seems untenable in the light of the evidence
brought forward by Ehrlich, Nernst, Michaelis, and others.
 Another view which seems to be gaining ground, as the analogy be
tween reactions of immunity and those of colloids in general is being
established more definitely, is that of According to this author. the
toxin does not combine with antitoxin according to the laws of pro
portions as typical for chemical reactions, but the antitoxin distributes
itself equally upon all the molecules of toxin present.Thus, if the
amount of antitoxin present is not sufficient to neutralize all of the
toxin, all of the molecules of toxin become partially saturated with the
antitoxin. Accordingly, there can be any number of degrees of satura
tion before a complete neutralization of toxin by antitoxin is reached.
This process can be likened, according to Bordet, to the saturation of
starch with iodin.The starch particles can absorb variable amounts of
Main and accordingly will present different intensities of color. Bordet
speaks of this process as being based on "adsorption" and not on
chemical combination between toxin and antitoxin.
Principles of first aid and anti toxic serum and its uses

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Principles of first aid and anti toxic serum and its uses

  • 1. PRINCIPLES OF FIRST AID IN HEALTH CARE
  • 2. First aid  First aid is defined as the immediate care given to an acutely injured or ill person. It can literally be life-saving so it behooves all of us to know some basic principles.What follows are some rules that cover common conditions and general practices: 
  • 3.  Don't panic. Panic clouds thinking and causes mistakes. First, do no harm.This doesn't mean do nothing. It means make sure that if you're going to do something you're confident it won't make matters worse. If you're not sure about the risk of harm of a particular intervention, don't do it. So don't move a trauma victim, especially an unconscious one, unless not moving them puts them at great risk (and by the way, cars rarely explode). Don't remove an embedded object (like a knife or nail) as you may precipitate more harm (e.g., increased bleeding). And if there's nothing you can think to do yourself, you can always call for help.
  • 4.  CPR can be life-sustaining. But most people do it wrong. First, studies suggest no survival advantage when bystanders deliver breaths to victims compared to when they only do chest compressions. Second, most people don't compress deeply enough or perform compressions quickly enough.You really need to indent the chest and should aim for 100 compressions per minute.That's more than 1 compression per second. CPR doesn't reverse ventricular fibrillation, the most common cause of unconsciousness in a patient suffering from a heart attack. Either electricity (meaning defibrillation) or medication is required.
  • 5.  Time counts.The technology we now have to treat two of the most common and devastating medical problems in America, heart attacks and strokes, has evolved to an amazing degree, but patients often do poorly because they don't gain access to that technology in time.The risk of dying from a heart attack, for example, is greatest in the first 30 minutes after symptoms begin. By the time most people even admit to themselves the chest pain they're feeling could be related to their heart, they've usually passed that critical juncture. If you or someone you know has risk factors for heart disease and starts experiencing chest pain, resist the urge to write it off. Get to the nearest emergency room as quickly as you can. If someone develops focal weakness of their face, legs, or arms, or difficulty with speech or smiling, they may be having a stroke, which represents a true emergency. Current protocols for treatment depend on the length of time symptoms have been present.The shorter that time, the more likely the best therapies can be applied.
  • 6.  Don't use hydrogen peroxide on cuts or open wounds. It's more irritating to tissue than it is helpful. Soap and water and some kind of bandage are best.  When someone passes out but continues breathing and has a good pulse, the two most useful pieces of information to help doctors figure out what happened are: 1) the pulse rate, and 2) the length of time it takes for consciousness to return.  High blood pressure is rarely acutely dangerous. First, high blood pressure is a normal and appropriate response to exercise, stress, fear, and pain. Many patients I follow for high blood pressure begin panicking when their readings start to come in higher. But the damage high blood pressure does to the human body takes place over years to decades.There is such a thing as a hypertensive emergency, when the blood pressure is higher than around 200/120, but it's quite rare to see readings that high, and even then, in the absence of symptoms (headache, visual disturbances, nausea, confusion) it's considered a hypertensive urgency, meaning you have 24 hours to get the pressure down before you get into trouble.
  • 7.  If a person can talk or cough, their airway is open. Meaning they're not choking. Don't Heimlich someone who says to you, "I'm choking."  Most seizures are not emergencies. The greatest danger posed to someone having a seizure is injury from unrestrained forceful muscular contractions. Don't attempt to move a seizing person's tongue. Don't worry— they won't swallow it. Move any objects on which they may hurt themselves away from the area (including glasses from their head) and time the seizure. A true seizure is often followed by a period of confusion called "post-ictal confusion."Your reassurance during this period that they're okay is the appropriate therapy.  Drowning doesn't look like what you think it does. For one thing, drowning people are physiologically incapable of crying out for help. In fact, someone actually drowning is usually barely moving at all (I strongly encourage everyone to click on this link to learn more about how to recognize what drowning does look like).
  • 8. antitoxic serum and its rules for uses  ANTITOXINSAn antitoxin is an antibody formed in an animal through the stimulation of a specific toxin.The usual method of producing an antitoxin is by the repeated injections of increasing amounts of toxine into a susceptible animal.The strongest antitoxins are obtained from animals that are very susceptible to the toxine, but all susceptible animals by no means produce antitoxins, although repeatedly injected with the appropriate poison.Thus, a guinea-pig which is very susceptible to diphtheria will not form diphtheria antitoxin, even after the repeated administration of diphtheria toxine. Guinea-pigs are also exceedingly susceptible to tetanus and react characteristically and violently to tet anus toxine, but the repeated injections of subminimal lethal doses of tetanus toxine into a guinea-pig do not immunize that animal, nor do they induce the formation of antitoxin. In fact, Knorr and also Behring and Kitashima have shown that guinea-pigs develop an increasing sensi tiveness to repeated injections of tetanus toxine instead of an increasing resistance. In other words, the guinea-pig, a susceptible animal, lacks the mechanism of antitoxin formation which is possessed in such a high degree by horses and other animals.Antitoxin produced by the horse or other animal when injected into the guinea-pig will protect it.
  • 9.  There are several reasons for selecting the horse for the production of immune sera for human use. On account of its size it furnishes large quantities of blood; the serum of the horse is the blandest blood serum of any known species; finally, the horse furnishes antitoxin in higher potency than any other known animal. Just how and by what cells antitoxins are formed in the body is not known.They are not formed directly from the toxines. In some ' way the toxine excites the cell to the formation of the antibody.The antibody leaves the cell and becomes "dissolved" in the blood and tissue juices. Perhaps the white blood cells (Metchnikoff), perhaps the con nective tissue cells (Ehrlich), are chiefly concerned.Within the body most of the antitoxin is found in the blood, but it also exists in greater or less concentration in practically all the fluids of the body and may also appear in the excretions, as the urine, saliva, milk, and bile.
  • 10.  Nothing definite can be stated concerning the chemical nature of antitoxins. Evidence strongly points to the fact that they belong to the higher proteins. In all probability antitoxins are globulins, at least they come down with the pseudo-globulin fraction from which they have not been separated.  Antitoxins are somewhat more stable than the toxines. Further, the toxines have a more complex constitution than the antitoxins.When the toxines deteriorate they change qualitatively as well as quantitatively.The antitoxins have a simpler constitution and deteriorate simply by a loss of power.  Antitoxins are destroyed by heat, acids, and many chemicals.They gradually deteriorate spontaneously when in solution.Thus, Anderson has found that the average yearly loss of the potency of diphtheria anti toxin at room temperature is about 20 per cent.; at 15° C. it loses about 10 per cent.; and at 5° C. about 6 per cent.There is little difference between the keeping qualities of untreated sera and concentrated sera. Dried diphtheria antitoxin kept in the dark at 5° C. retains its potency practically unimpaired for at least years. Antitoxic sera should always be kept in a cool, dark place.While antitoxin loses some of its potency with time, and while recently tested sera of known unit value are always desirable, there is absolutely no reason why a serum, however old, should not be employed provided a fresh supply is not at hand. It should be remembered that antitoxins deteriorate quantitatively only ; in other words, an old antitoxin is quite as useful in proportion to its unit strength as a fresh serum; in fact, antitoxic sera are frequently two years old when placed upon the market by manufacturers.
  • 11.  Antitoxins are strictly specific; that is, they neutralize the corre sponding toxine and have no other apparent action within the body.The occasional ill effects, such as the serum sickness, following the injec tion of antitoxic sera, are due to other substances (the proteins in the serum) and not to the antitoxins themselves. Tulloch 24 on the basis of agglutination tests has separated tetanus cultures into four types., For tunately, any one of the four antitoxins will neutralize any or all of the four toxins. It is, however, advisable to prepare the antitoxin with the four different types.  Antitoxins may be injected subcutaneously, intravenously, into the subarachnoid space, into muscle, into the brain substance, or into any of the body cavities. Antitoxins are practically useless when given by the mouth, as very little is absorbed. Antitoxins when injected into an organism disappear rather quickly. Some of the antitoxin is bound to the corresponding toxine, if any is present, some combines with the cells, but the greater part is eliminated as antitoxin in the urine, bile, saliva, etc.The antitoxin produced actively by the body as a result of an attack of disease, or stimulated by the injection of toxine, is formed continuously and confers an immunity for an indefinite period. Passive or antitoxic immunity is, on the other hand, transient; it cannot be de pended upon for more than ten days or two weeks.  Some persons have sufficient native antitoxin in their blood to pro tect them against diphtheria.This has been demonstrated through the Schick reaction (see page 201). In such cases the antitoxin is pro duced naturally for long periods, often during the life-time of the in dividual.  When antitoxic serum is injected subcutaneously the antitoxin is absorbed slowly. It requires about 48 hours under these circumstances for the antitoxin to appear in the blood in maximum amount.There fore, when very prompt action is desired, the antitoxic serum may be introduced directly into the circulation by intravenous injection.  There are a number of antibodies that are either true antitoxins or closely resemble these antibodies. Some of these antibodies neutralize the true bacterial toxines, others the poisons of animal origin, others the poisons of plant origin, and others neutralize the activity of fer ments. The principal antitoxins, according to this classification, are brought together as follows: (1) Bacterial Antilosins. The three principal and most potent bac terial antitoxins are those of diphtheria, tetanus, and botulinus. The following are also considered to have antitoxic properties: pyocyaneus. symptomatic anthrax, antileukocidin and antilysin against bacterial hemolysins.
  • 12.  (2) Animal Antitoxins.These antitoxins are produced by animal poisons belonging to the venoms.True antibodies are obtained against snake venom and similar poisons in spiders, eels, wasps, scorpions, fish, salamanders, and toads.  (3) Plant Antitoxins.These are antiricin, antiabrin, antirobin, and anticrotin.  (4) Ferment Antitoxins. Antibodies may be obtained against fer ments, such as pepsin, urease, rosinase, steapsin, trypsin, fibrin ferment, lactase, cyranase; and antibodies may also be obtained against the en zymes found in bacterial cultures.
  • 13.  There are comparatively few antitoxic sera of practical use in human therapy, just as there are relatively few true bacterial toxines.The best known antitoxins are those of diphtheria, tetanus, and botulinus. Numerous other antitoxic sera are found upon the market or have been described, but they are of doubtful value.  Antitoxins are valuable both as curative and immunizing agents. Their preventive action depends upon the fact that they meet the toxin. unite with and neutralize it, thus rendering it harmless.As already stated, the antitoxins remain in the body a brief time and their immuniz ing power, while of a high grade, is transitory.They disappear in about ten days or two weeks; the immunity must, therefore, be renewed in special cases by repeated injections of the antitoxin until the danger is passed.This phase of the subject is considered in more detail under the prevention of diphtheria and tetanus.The usual immunizing dose for diphtheria is 1,000 units, for tetanus 1,500 units.
  • 14.  As a curative agent antitoxin must be administered early and in sufficient amount to insure success. It is most important to give the antitoxin early— before the damage is done.Too great emphasis cannot he laid upon this point. After the toxin has united with the cells it cannot be dislodged by the antitoxin.The importance of giving anti toxin early is well illustrated in the case of diphtheria.When moder ate amounts (3,000 to 10,000 units) are injected on the first day of the disease the mortality is practically nil.The mortality increases with each hour's delay.  The importance of giving this sovereign remedy early is also illus trated in the experiments of Rosenau and Anderson 25 upon the influ ence of antitoxin upon postdiphtheritic paralysis. It was found that one unit of antitoxin, given not less than 24 hours after a fatal dose of diphtheria toxine in a guinea-pig, greatly modified the postdiph theritic paralysis and saved the life of the animal, whereas 4,000 units riven 48 hours after the infection did not modify the paralysis or save the life of the animal. Four thousand units of antitoxin is an enor mous amount for a guinea-pig weighing about one-half pound. Weight for weight, it corresponds to 400,000 units for a 50-pound child.The fact that one unit of antitoxin saves life when administered timely; whereas enormous doses fail totally when delayed, should be sufficient to place physicians on their guard ; increased dosage cannot atone for delay.When cases are seen late in the progress of the disease it is good practice to give the serum intravenously, so as to neutralize the toxin at once and prevent further damage. If given subcutaneously, further delay results on account of the time necessary for absorption.Tetanus antitoxin is a very valuable immunizing agent, but is of less value after symptoms have appeared, for then most of the damage has been done.
  • 15.  Preparation of Antitoxin.The antitoxin used in human therapy is practically always contained in the blood serum or blood plasma of the horse.The blood is drawn from the jugular vein into sterile bottles.The bleeding should never be done until a week or more has elapsed after the last injection of toxine, so as to allow time for the disappearance of the poison from the circulation.The horses are given no food for about 24 hours preceding the bleeding, so that the blood may not contain the fresh products of digestion and metabolism.After the blood is drawn it may be allowed to clot spontaneously. In the case of horse blood this takes place more quickly at room temperature than in the ice cheat.  The clot is allowed to contract for a few days and the serum containing the antitoxin is then drawn off with a pipet or simply decanted. In this way a.clear transparent serum is obtained which, if protected against contamination by the usual bacteriological precautions, is sterile and may be preserved indefinitely. It is almost a universal practice, however, to add a preservative; either chloroform (0.3 per cent.), phenol (0.5 per cent.), or cresol (0.4 per cent.).These preservatives in the amounts named are harmless when injected and have practically no effect upon the antitoxin itself.They gradually precipitate the albuminous matter from the serum, which settles as a white amorphous deposit and which may be disregarded, as it is harmless.Chloroform produces a better looking serum, but the less volatile preservatives are usually preferred on account of their stability and, hence, greater reliability.
  • 16.  By the method of allowing the blood to coagulate, as above described, only about one-third of its volume is recovered as antitoxic serum. A much greater yield ,may be obtained by citrating the blood.: sodium citrate prevents the clotting of blood. A solution of this salt is placed in the bottle which is to receive the blood directly from the horse, in sufficient amount to be present in 1 per cent. of the whole blood.The corpuscles soon settle to the bottom, leaving the clear supernatant plasma, which is then decanted or drawn off with a pipet. In this way the yield of antitoxic fluid is about 90 per cent. of the volume of the blood, and is. therefore, preferred to the less economical method of allowing the blood to clot.  The citrated plasma may further be "purified" or concentrated by various methods, that generally used being a modification of Gibson's " method, based upon the earlier experiments of Atchinson.  Ordinary antitoxic serum contains serum globulins (antitoxic), serum globulins (non-antitoxic), serum albumins (non-antitoxic), serum nu cleoproteids (non-antitoxic), cholesterin, lecithin, traces of bile color ing matter, traces of bile salts and acids, traces of inorganic blood salts, and other non-proteid compounds. Refined serum contains serum globulins (antitoxic), traces of serum globulins (non-antitoxic) dissolved in dilute saline solution.
  • 17.  Method of Concentrating DiphtheriaAntitoxin.The Banzhaf modification of the original Gibson method for concentrating antitoxic serums is based on the fact that the antitoxin is contained in the pseudo globulin fraction of the serum, and has as its purpose the isolation of the antitoxic pseudoglobulin from the non-antitoxic euglobulin, albumin and other serum constituents. Plasma, instead of serum, is used for reasons of convenience and economy. By adding ammonium sulphate to the diluted plasma up to about 30 per cent. saturation and heating the mixture to 60° C., the euglobulin and converted non-antitoxic pseudo globulin are precipitated, and removed by filtration. By raising the saturation of the filtrate to about 50 per cent. with ammonium sul phate, the antitoxin is precipitated.This is collected on filters, pressed, and dialyzed in parchment bags until all the antitoxin is in solution and free from ammonium sulphate. It is then neutralized and brought to isotonicity with the blood by sodium chlorid, and a preservative added. It is filtered first through pulp and finally through a Berkefela filter.  This method entails a loss of about 25 per cent. of the antitoxic units, but results in a five- or six- fold concentration of the antitoxin.The process of concentration makes it possible to utilize serum of low potency; it enables one to give large doses of antitoxin in small volume; and eliminates the bulk of serum proteins responsible for reactions and for serum sickness.  Mode ofAction.The mode of action of antitoxins is now fairly well understood. One thing is certain, and that is that the antitoxin unites directly with the toxin.This may be readily demonstrated by adding a little antitoxin to some toxin in a test tube and then injecting the mixture into a susceptible animal; no symptoms result. Diphtheria antitoxin combines with diphtheria toxin more quickly than tetanus an titoxin combines with its toxin.Thus, in the case of diphtheria the union between the toxin and its antibody is complete in less than twenty minutes at room temperature, while in the case of tetanus it requires one hour.These facts are of practical importance in the work of standardization, in which case the toxines and antitoxins are mixed in the test tube and the combining action must be complete before the mixtures are injected into the test animals in order to insure accurate results.
  • 18.  Ehrlich believes and strongly defends his assumption that an anti toxin unites with a toxin just as an acid unites with an alkali, that is, the one has a strong chemical affinity for the other, and the union is simple and direct.The reaction is complicated only on account of the complex nature of toxine. According to Ehrlich, there are two primary metabolic poisons in a filtrate of a culture of B. diphtheriae: (1) toxin, a poison which produces a local destruction of tissue and acute death; and (2) lozon, a nerve poison that produces late paralysis.There is also a modified toxin, known as toxoid.Toxin is more actively poison ous and also has a greater affinity for antitoxin than toxon, which it is able to displace from its combination with antitoxin.This explains in part the discrepancy between the IA, and the doses. Ehrlich believed that the union of filtrate with antitoxin seems to occur in multiple pro portions resembling valancies.  On the other hand, Arrhenius and Madsen insist that, instead of considering the toxine as a complex mixture of various substances, such as a toxin, toxon, etc., it would be simpler to consider it as a single (at least homogeneous) substance which has a very weak affinity for the antitoxin and that in mixtures containing toxin and antitoxin there are always both free toxin and free antitoxin. Arrhenius draws his analogy from known facts in physical chemistry, particularly from studies upon the relation between solutions of boracic acid and ammonia.These two substances have a comparatively weak affinity for each other, and in mixtures all the boracic acid does not combine with all the am monia, but there are always present both free ammonia and free boracic acid.
  • 19.  When ammonia and boracic acid are brought together in watery solu tion some of the ammonia at once unites with some of the boracic acid to form ammonium borate.This reaction starts with a certain velocity, but as the mass of ammonium borate increases the velocity of the reaction gradually diminishes.After a time a condition is reached when the ammonium borate has a maximum value and does not further increase, no matter how long the reaction is allowed to proceed under the given conditions.  When this condition of equilibrium is reached the mass contains a certain quantity of water, ammonia, boracic acid, and ammonium borate; but these substances are not at rest.The ammonia and boracic acid will always react when in the presence of each other, whether or not am monium borate is present. But, as the appropriate amount of ammonium borate remains constant, it is understood while this continuous association between the ammonia and the boracic acid is going on there is at the same time a reversible action—that is, a dissociation of the ammonium borate to re-form ammonia and boracic acid.These two reactions take place simultaneously.
  • 20.  Arrhenius believes that the diphtheria poison changes slowly accord ing to the laws of monomolecular reactions, that the toxin combines feebly with the antitoxin, the equilibrium constant being equal for both.The claim, however, that the toxin is a simple substance having a weak affinity for the antitoxin and that the combination of toxin and antitoxin follows the Guldberg-Waage law, and that the reaction is, therefore, reversible, seems untenable in the light of the evidence brought forward by Ehrlich, Nernst, Michaelis, and others.  Another view which seems to be gaining ground, as the analogy be tween reactions of immunity and those of colloids in general is being established more definitely, is that of According to this author. the toxin does not combine with antitoxin according to the laws of pro portions as typical for chemical reactions, but the antitoxin distributes itself equally upon all the molecules of toxin present.Thus, if the amount of antitoxin present is not sufficient to neutralize all of the toxin, all of the molecules of toxin become partially saturated with the antitoxin. Accordingly, there can be any number of degrees of satura tion before a complete neutralization of toxin by antitoxin is reached. This process can be likened, according to Bordet, to the saturation of starch with iodin.The starch particles can absorb variable amounts of Main and accordingly will present different intensities of color. Bordet speaks of this process as being based on "adsorption" and not on chemical combination between toxin and antitoxin.