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Since the initial injection of the crude toxin often gives rise to quite severe local as well as systemic reactions, various attempts have been made to modify the material so as to diminish this feature as far as possible without interfering with its antigenic (stimulating) value. Several methods are available for attenuating (weakening) the toxin for injection purposes, but the one most commonly selected is the "simultaneous” method, especially in tetanus antitoxin, where a mixture of toxin and an excess of antitoxin is given in the initial injection. The result of this injection of toxin is usually followed by a rise in temperature, loss of appetite and a loss in weight of the animal. After the reaction from such an injection has completely subsided, a second injection without antitoxin is given and so on, the interval between injections being about three days and depending upon the reaction of the horse and the speed with which it entirely recovers from the preceding injection. The immunization is continued with increasing doses of toxin given by itself and at intervals of three to seven days, until at the end of three or four months as much as 250 to 500 c. c. of unaltered toxin is given at one time. When the injection of large quantities of the toxin has been reached, the productive period of the horse is expected to begin. Usually as the doses of the toxin are increased, the antitoxicity of the blood also increases, though this is not always the case, for occasionally horses have been treated by injections of the toxin for as long a period as two years without producing a serum of high antitoxic potency. In most cases, however, the horse is thoroughly immunized by the end of three or four months, at which time "trial bleedings" are made. If the test shows that the antitoxic content of the blood is sufficiently high the horse is ready for regular "bleedings."
If the serum is to be concentrated, the horses are bled aseptically from the jugular vein into bottles or jars containing a solution of some citrate or oxalate, which prevents the clotting of blood. From six to eight litres of blood are withdrawn at each bleeding. The intervals between bleedings are from six to twenty-four days, the custom not being the same in different laboratories. The more conservative method is to bleed every three to four weeks. The bottles of blood are set aside for two to three days in a cool, dark place to allow the corpuscles to settle. At the end of this time, the clear serum or plasma is siphoned into sterile bottles and stored in the refrigerator. If it is desired to keep the serum for some time before refining, it is preserved with a small percent of chloroform. Also it is customary to immunize several horses at the same time, for experience has shown that the serum of certain animals contain substances, which cause rashes in man. “Pooling” the blood reduces this possibility.
When the globulins are to be separated, the antitoxic serum as obtained from the horse directly may be refined and concentrated. Gibson in 1905 was the first to introduce a method of commercial value for the concentration of antitoxic horse sera. Later, Gibson and Banzhaf devised several methods for the refining and concentration of diphtheria antitoxin. Most establishments are employing the method developed by Banzhaf in 1912, in which he has reduced the proportion of non-specific protein as far as is practical by purely chemical agents. This process involves an extensive application of chemical means to acquire the desired product. Heinemann also has worked out a process by which a combination of the methods of Gibson and Banzhaf yields an exceptional high rate of concentration. As yet, in a general way, this method has not been adopted by manufacturers.
When the antitoxin has passed through the last stage of concentration, it is purified by the addition of a preservative (trikresol) and subjected to a final filtration through a Berkefeld Pressure Filter. To endure the safety of the product numerous “sterility" tests are made to determine its freedom from bacterial contamination. Following this its antitoxic strength is tested on a series of guinea pigs to ascertain its potency in terms of units. When this is determined the antitoxin is ready for distribution and use.
The chief advantages accruing from the refining and concentration of antitoxin are: that the final product has greater stability, and the fact that a smaller quantity of serum is required for injection, and that from a three- to a four-fold concentration is really obtained. It is also possible to obtain the same therapeutic effect by the injection of about one-third the amount of solution when concentrated antitoxin is administered.
Diphtheria antitoxin is furnished in aseptic vials and glass syringe packages ready for immediate use. The return date is six months to two years according to varying customs in the different laboratories, and according to various amounts of excess put into the packages. Before this finished package is allowed to be placed on the market, the product must be subjected to repeated bacteriological and physiological tests to insure its purity and unit strength according to the standard adopted by the United States Public Health Service.
NEGRO HEALTH WEEK.
In the first call for the National Negro Health Week which is to be observed April 21 to 27, 1917, reference was made to the cooperation of the National "Clean Up and Paint Up" Campaign bureau, Kinloch building, St. Louis, Mo.
In addition to their offer to send literature to any community where health week campaigns may be observed they have now offered three prize cups for the best clan up effort among the negro people.
The conditions of the contest together with names of the judges will be published later. Local committees and campaign chairmen desiring to enter their communities for these cups should make known their intentions to Emmett J. Scott, secretary, Tuskegee institute, Alabama. He will also be very glad to send detailed plans and suggestions for conducting health week campaigns.
ACETANILID IN COLD MEDICINES.
J. S. McCune. Chief Chemist, Ohio State Board of Health, "Overdose in Pill Causes Death” was the headline of an item in a recent issue of a Columbus paper. It was stated that the coroner had found that the death of a Detroit man in a Columbus hotel was due to the use of a cold medicine containing acetanilid. The case is not unique, but it shows the carelessness in the use of this drug.
Acetanilid, or antifebrin, is of value because of its effects upon the temperature conditions of the body. But it is not a drug to be taken unknowingly or thoughtlessly. Statements of its presence and amount are required by law upon drugs, and such statements should be noticed and considered by anyone using cold or headache medicines. Its reckless use is very apt to cause disturbance and collapse and may cause death. The table following shows the amount of acetanilid present in some of the cold medicines upon the market. The acetphenetidin tablets are appended because acetphenetidin, or phenacetin which is the name it was patented under, is similar to acetanilid in its uses and effects. Antipyrine and lactophenetidin are other similar drugs. The general remarks following the table apply to all of these, altho acetanilid is considered the most toxic of the group
Casco Cascara Bromide Quinine
0.50 0.5) 0.9 1.03 1.3 1.34 1.68 2.07 2.95
Acetanilid was not declared per tablet but as 54 grains per ounce. The amount found was 52.6 grains per ounce, which showed 0.51 grains per tablet.
** Trace of alkaloids present in these tablets,
Analyses by J. L. Russell, Chemist, State Board of Health.
The above are all cold medicines now upon the market in Ohio, purchased and submitted for analysis by the inspectors of the Ohio Dairy and Food Bureau in the course of their active service in the enforcement of the food and drug law of Ohio under the direction of T. C. Calvert.
In one of the medicines listed above, Krause's Cold Capsules, it will be seen there are three grains of acetanilid per tablet. The directions on the box are as follows:
"For an adult take 1 capsule every 3 hours during the day. Before retiring take 2 capsules. Then take 2 or 3 capsules a day".
If the tablets were started in the morning and the directions followed, twenty-one grains of acetanilid would be taken the first day—undoubtedly a dangerous amount.
To explain why acetanilid should be used with caution let us consider briefly its effects. First, it decreases the heat production and to some degree increases heat loss, the temperature effects desired. But it is a depressant, by some considered as acting directly upon the heart, altho this is denied by others and its depression effects attributed to circulation failure. Five grains have been known to cause death, and collapse may occur with susceptible persons from a medicinal dose of one or two grains. The amount producing dangerous symptoms varies with the individual according to his tolerance. A toxic dose produces profuse perspiration, vomiting, cyanosis, chills, convulsions and paralysis of muscles and motor nerves. In addition to the effects of overdose there is the injury to the red corpuscles of the blood caused by continuous use, and degeneration of the heart, liver and kidneys. Acetanilid habit has been observed with weakened heart, blue membranes, and moral degeneration similar to the morphine habit. This is rare, however, and the real danger comes from overdose.
In case of such overdose antidotes may be given and measures taken to prevent death. Evacuation of the stomach, artificial respiration, and application of heat are of value, and strychnine, digitalis, caffeine citrate, or oxygen should be administered.
But rather than treatment of collapse let us use care to prevent it. Before taking cold tablets or headache mixtures, if one must use such medicine without the advice of a doctor, look at the labels carefully and consider what the statements mean. The laws for branding foods and drugs are not technical traps to catch manufacturers, they are plans to inform and help the consumer. Unfortunately the consumer only too often never even reads the labels. They should not only be read, they should be studied and their meaning appreciated. Where acetanilid is stated, and the above analyses show that it is generally correctly stated, consider how many grains are going to be taken, and do not follow directions blindly. In other words, look for acetanilid on the label of such a medicine, if you use it, and if found consider it marked "Handle with Care."
SHE ASKED FOR MORE BUGS IN THE MILK.
"There's no such thing as too much instruction,” said Health Commissioner Selby of Toledo, recently.
A woman telephoned to him and said she had quit dealing with her milkman because the bacteriological count in his milk is too low.
The physician explained the difference between high and low. Toledo Blade.
DAILY HEALTH CHART FOR CHILDREN. Assistant Health Officer Peters of Cincinnati will ask School Superintendent Condon to place a chart containing a daily health guide for boys and girls in every classroom in the public schools. The chart reads:
MORNING: Eat slowly. Walk (don't run) to school.
BREAKFAST: Fruit, cereals and plenty of milk, eggs, bread and butter. No coffee or tea at any meals. Brush teeth.
SCHOOL: Going and coming take 10 deep breaths slowly with shoulders straight and head up. Don't sneeze near another person. Use your handkerchief. Don't spit.
NOON: Wash hands and face. Use soap. Glass of water before eating
DINNER: Besides meat and potatoes, or rice, eat plenty of vegetables. Eat plain puddings or fruit. Chew each mouthful thoroughly.
AFTERNOON: Walk slowly after eating. Keep cheerful. Play out of doors after school.
EVENING: Clean up. Glass of water.
SUPPER: Plenty of milk, fruit. Eat fish or eggs instead of meat. Fried foods are hard to digest.
NIGHT: Windows open top and bottom. Sleep out of doors when you can.