A FURTHER SHORT PROVING OF SULFANILAMIDE


The chief difficulty encountered was the obtaining of suitable persons as provers. In this instance only two people were considered sufficiently fitted for this experiment. One was a young man of 26, the other a married mother age 31. I, myself, refrained from taking the drug because at the time I showed enough symptoms of a chronic nature that I felt a true picture of the drug action could not be obtained.


Two years ago I presented a paper entitled Sulfanilamide: A Fragmentary Proving. During the past few months I have conducted a supplementary proving of the same drug, a report of which constitutes the body of the present writing.

The chief difficulty encountered was the obtaining of suitable persons as provers. In this instance only two people were considered sufficiently fitted for this experiment. One was a young man of 26, the other a married mother age 31. I, myself, refrained from taking the drug because at the time I showed enough symptoms of a chronic nature that I felt a true picture of the drug action could not be obtained.

Both the male and the female prover were given the two hundredth centesimal attenuation of Sulfanilamide, a single dose being taken in the morning before breakfast. This initial dose was allowed to act undisturbed as long as any symptoms traceable to its influence were observable. No interference was made in the provers normal mode of living. In other words, no artificial set of conditions was set up under which the experiment was to be conducted, because I desired to see whether a drug disease could occur under the same circumstances as a natural disease occurs, that is, during the course of the individuals normal routine of life.

In order to allow a better particularization of what happened to each prover during the experimental period, I shall take up each in order.

C.W., Jr., age 26, male, was given Sulfanilamide 200, one dose, on April 22, 1942. There were no symptoms developed as a result of this dose. Therefore on May 5, 6, and 7 he was given Sulfanilamide 200, one dose. No reaction was observed and it was concluded that this prover had not sufficient susceptibility to the potency used to enable him to develop symptoms.

With this thought in mind, it was decided to repeat the experiment, using a lower potency of the drug. Therefore, on May 13 the prover was given Sulfanilamide 3x., a tablet triturate prepared by Boericke & Tafel from crude sulfanilamide obtained from Merck & Co. The instructions were to take a dose every two hours beginning with one tablet and increasing one tablet with each succeeding dose until he was taking five tablets at a time. A total of fifteen tablets was taken.

No symptoms were manifest until the following day, May 14, when at 3 p.m., following a cold drink, there suddenly appeared a “sore throat”! This complaint involved the right tonsil. There was no description by the prover as to the character of the pain, except that he stated that this throat was “very sore.” There was definite amelioration from hot liquids and just as definite an aggravation from swallowing cold water. Additional modalities were to the effect that empty swallowing was more painful than swallowing solid food. The soreness lasted until he went to sleep at 9:30 p.m. and was completely gone the next morning.

Accompanying the pain were swelling and redness of the right tonsil. In addition there was soft, non-painful swelling of the right cervical glands. A contradiction appeared on May 15, the following day, in that the cervical glands were more swollen after sleep, though still not painful. However, the tumefaction gradually decreased during the day and was gone by nightfall.

On June 1 the prover again took Sulfanilamide 3x in the same manner and amount as previously described but no symptoms resulted. The experiment was repeated on June 5, a total of twenty tablets of Sulfanilamide 3x. being ingested, and again no symptoms resulted. The prover was therefore requested to discontinue the experiment.

The story obtained from the female prover paints a picture of rather definite reaction to the drug which manifested itself through the gastrointestinal system, genital sphere, sensorium, skin and extremities. The written report from the prover is rather verbose, therefore I shall condense it into its essential features.

One powder of Sulfanilamide 200 was taken March 25, 1942, before breakfast-time not mentioned. No symptoms were evident until 1:00 p.m. on March 27 when there began a period of tasteless eructations lasting until 3:00 p.m. March 28. These eructations were definitely aggravated when talking. In fact the prover was uncertain, whenever she opened her mouth, whether she would “burp” or bellow-a situation faintly analogous to that produced by Aloes at the distal termination of the intestinal tract!.

Although the above symptom ceased at the time mentioned, it was succeeded by an even more embarrassing one, to wit, “the gas began going down.” Need I say more? Sudden emission of odorless flatus at any time of day or night lasted for six days “without regard,” the prover stated, “to where you might be.” There was no warning, just an explosion, induced particularly by any change of position such as stooping, bending or squatting. No pain accompanied this manifestation, the only discomfort being “bloating” or full feeling in the abdomen after eating, especially after eating lunch.

Just about the time the provers intestinal symptoms were going full blast (!), namely on March 30, there also developed the beginning of a series of eruptions- I refer now to skin eruptions-which lasted until the proving was terminated, a period of four weeks and two days.

It seems appropriate to state here that the prover was obliged to discontinue the experiment on April 28 because she developed a marked laryngitis. I could not be certain whether this was drug action or natural disease. Therefore it was thought best to disregard all symptoms developing during and following this illness.

Let us return now to the skin symptoms. The first of these appeared as an itching red “rash” appearing on face, neck, scapular regions the first day, about the upper abdomen the second day, about the region of the navel the third day. By the sixth day the “rash” had disappeared save for scratch marks. One modality observed was that the itching was ameliorated from washing in hot water; another was: “After scratching, burning.”.

At the same time, apparently, washing in hot water brought out more eruption.

On April 5, the day following the subsidence of the eruption just described, at 3:00 p.m., a different type of skin manifestation began its development. A smarting, burning papule would make its appearance upon an inflammatory base. In a few hours the papule became pustular, then several more papules would grow around the periphery of the original lesion. They healed in the reverse order. All very “sore” until they opened. In addition a “blind boil” the size of a dime appeared on the chin lasting over three days, very tender and having a continual pulling sensation. A few of the papules appeared between the scapulae.

A week later, April 12, itching papules began to appear on the inner side of the right leg thickest near the knee. They easily broke down with scratching, leaving scabs. a peculiar eruption below the knee described by the prover as “little cores that seem to raise up and you pick them off (more fun)”.

The anal region was next involved-papules smarting and burning. Apparently these became pustular and opened, for the prover says she “felt wet and very sore.” Likewise some superficial ulceration must have occurred, for the prover spoke of “red sores with no heads” which itched. Soreness, smarting and burning were the chief sensation, aggravated by exertion and walking, ameliorated from bathing parts in hot water.

The perianal lesions lasted over a week. The prover has this comment to make, “I used to have this trouble dating back to a kid eight years old when I had that kidney trouble. . . only then it used to cause large sores. . . as the kidney trouble got better, the itching and breaking out stayed on. This was really cleared up by Sulphur and I have had almost none of it in the last five or six years”.

On April 20 some more “pimples” on the face with sensation of stinging and pressing outward.

On April 22 a papule erupted on the inner side of left knee with pricking-outward sensation. The power remarked, “It feels as if I had a piece of steel in it and . . .even scratched my other leg when I walked. Eventually she dug out a little hard core.

On this same day a sudden attack of syncope appeared after breakfast, which was relieved by sting bent forward. The prover reported, “I got up dizzy and a little sick to stomach”.

She felt too hot and immediately another syncopal attack occured, relieved in the same way. “Dizziness” persisted all the morning, described as a wave of heat from stomach to head followed by vertigo; felt as if heard were whirling and there was a sensation as if she would fall to the left. These symptoms were better in the open air, by sitting with head low, or merely by sitting.

On April 20 the prover stated that a great deal of the soreness of the spine which had been present for the past year had disappeared.

With respect to the genital sphere, the symptoms recorded were not many. The prover definitely reported sudden onset of menses in the morning. As a rule she exhibited a scanty flow with much pain and backache and many small clots; pain, backache, scanty flow and small clots always going together. Under Sulfanilamide the picture was different: Colicky pain in lower abdomen the day before menses, then sudden onset of flow which was profuse with more small clots than usual but not much discomfort.

The manifestation of drug action occuring in the extremities affected the muscles of the calves, especially the right calf. The effect was described as “cramps.” They began on April 13 following a misstep, to which mishap she attributed them. However, they continued until the experiment was terminated. The cramps always appeared from 6:00 to 12:00 p.m., while walking or standing, never at rest, and were ameliorated by rubbing the part.

Whether any conclusions can be drawn, based on these two rather incomplete provings of Sulfanilamide, as to the drugs therapeutic usefulness when prescribed according to the Law of Similars, can be determined only by further experiments of a similar nature. However, there has been shown, both in the 1940 proving and the present one, a definite relationship between Sulfanilamide and various types of skin lesions. Nothing very characteristic of the remedy seems to have been established unless it be “suddenness”: sudden vertigo, sudden onset of eruption, sudden onset of menses, sudden sore throat. In addition there appeared to be rather definite amelioration from open air and, in respect to itching , amelioration from hot bathing.

The schema appended is the same used in the 1940 proving with new symptoms added. As before, rubrics marked “T” indicate manifestations appearing in patients under treatment with crude sulfanilamide those marked “P” were developed in the provers. The numerals “40” and “42” are placed after “P” to distinguish between the symptoms of the earlier proving and the present one.

SCHEMA

MIND.

Dullness. T.

Confusion. T.

Loss of memory, accompanied by deafness. T.

Sensation similar to alcoholic intoxication. T.

SENSORIUM.

Vertigo. T.

Lightheadedness, as if drunk. T.

Lightheadedness, aggravated by smoking, ameliorated in the open air and when thinking of other things. P-40.

Faintness after breakfast, better by sitting bent forward, followed by vertigo and nausea. P-42.

Vertigo: Worse in the house, better in open air; accompanied by nausea; preceded by wave of heat from stomach to head with sensation as if head were whirling, and as if she would fall to left, better sitting bent forward; on entering warm room from open air. P-42.

INNER HEAD.

Headache. T.

Dull ache in the occiput with ringing in the ears, better in the open air. P-40.

Fullness and heaviness, as if cold would appear, worse in a.m. P- 40.

OUTER HEAD.

Pustules on forehead.P-40.

Soreness of the forehead.P-40.

Red, macular eruption right temple. P-42.

Pustular “whitehead” in hair above right ear. P-42.

Itching: of eruption on right temple; after scratching or

rubbing, burning; better by bathing in hot water. P-42.

Smarting and burning of pustule over right ear, better when discharging. P-42.

EYES.

Hard, red pimples with yellow tips on right eyebrow. P-40.

Red swelling on margin of left lower lid at inner angle. P-40.

Red swelling on margin of left lower lid at inner angle. P-40.

Stye at inner angle of left lower lid covered with several small yellow pimples. P-40.

Left sclera “very bloodshot.” P-40.

Sensation about left eye as from “little pin pricks,” especially on inner angle of lower left eyelid. P-40.

Swelling of both upper and lower left eyelids accompanying stye. P-40.

EARS.

Tinnitus. T.

Ringing in the ears accompanying dull ache in the occiput. P-40.

Stuffiness in the ears, relieved in the open air. P-40.

NOSE.

Scanty, watery discharge in the morning. P-40.

Yellow pimples on inside of left nostril. P-40.

Scabby sore on inside of left nostril which discharge bloody serum, worse when blowing nose. P-40.

Stinging over bridge of nose in the morning. P-40.

Red swelling on left side of bridge. P-40.

“Sore” on edge of left nostril covered with soft yellow scabs which discharges serum or blood. P-40.

Similar sore on edge of right nostril. P-40.

Pimples on the nose. P-40.

Pustule in the crease beside the left nostril, smarting, better when discharging. P-42.

Smarting and burning of “sore” on nose, worse from touch; better from heat and when discharging. P-40.

Sneezing. T.

FACE.

Pustules on the forehead. P-40.

Soreness of the forehead. P-40.

Papule over left zygoma surrounded by three others on an inflamed base, sore, aggravation from touch. P-42.

Burning-smarting papule in front of left ear becoming pustular, worse from touch, better when discharging. P-42.

Pimples on cheek near left nostril. P-40.

Skin-colored papules on left cheek on red base, stinging, accompanied by pressing-outward sensation. P-42.

Red pimple behind angle of left jaw, soreness, appeared during menses and after taking cold. P-40.

Sore, red pimple on chin. P-40.

“Blind boil” on chin, very sore, worse from touch, accompanied by pulling sensation. P-42.

Brown, pigmented spot behind angle of left jaw after pimple had healed. P-40.

MOUTH.

Peculiar taste in mouth as after inhaling hydrogen sulphide. P-40.

Pricking sensation on the tongue, as if fine needles were touching it. P-40.

DESIRES, AVERSIONS.

Anorexia. T.

STOMACH.

Nausea and vomiting. T.

Indigestion. T.

Noisy, tasteless eructations, worse when talking. P-42.

ABDOMEN.

Colicky abdominal pains. T.

Colicky pains in lower abdomen the day before menses. P-42.

Aching low down in pelvic portion of abdomen, as if menses would appear. P-40.

Bearing down sensation in pelvis. P-40.

Sensation in lower abdomen as if menses had appeared. P-40.

Full feeling in abdomen, worse after eating. P-42.

Full feeling in abdomen, worse after eating lunch. P-42.

Sudden emission of odorless flatus, worse from any change of position. P.42.

Itching, macular eruption just above the navel. P. 42.

Hepatitis and jaundice. T.

STOOL and ANUS.

Diarrhoea. T.

Constipation. T.

Eruption about anus, smarting and burning. P-42.

Moist eruption about anus, very sore. P-42.

Itching “sores” about anus. P-42.

Smarting and burning about anus worse from exertion, better from bathing in hot water, coating with vaseline. P-42.

Recurrence of old perianal irritation supposedly cured by Sulphur. P-42.

URINARY.

Slowing of and loss of force of urinary stream. T.

Micturition difficult. T.

FEMALE.

Menstrual flow less than usual. P-40.

Menstrual flow more profuse than usual. P-42.

Many small clots in menstrual flow. P-42.

Sudden onset of profuse menstrual flow.P-42.

Before menses: Aching in back and down legs to ankles; bearing down in the pelvis; aching in pelvic region; sensation in pelvis as if menses had appeared; aching in right leg. P-40.

Before menses: Colicky pain in lower abdomen the day before. P-42.

During menses: Red, sore pimple behind angle of left jaw. P-40.

During menses: Less pain than usual; flow more profuse than usual. P-42.

BREATHING.

Dyspnoea. T.

Persistent dyspnoea. T.

Hyperapnoea. T.

Asthma. T.

Cyanosis. T.

Pain in the chest. T.

HEART.

Tachycardia. T.

NECK AND BACK.

Red, macular, itching eruption on sides and front of neck, better bathing in hot water; after scratching, burning. P42.

Red, macular, itching eruption over left scapula, better from bathing in hot water; burning after scratching or rubbing. P-42. Smarting-burning papules between scapulae, worse from touch. P-42.

Aching in the back of the neck coming from the shoulder, worse when lying down. P-40.

Improvement of soreness of dorsal spine which had been present over a year. P-42.

Aching in the lower back before menses. P-40.

LIMBS.

Lameness in belly of right triceps, worse on beginning motion, better from continued motion and from rest. P-40.

Stiffness of right arm in the morning with lameness, aggravation from raising arm above head. P-40.

Aching in shoulder (right) proceeding up back of neck, worse when lying down. P-40.

Tingling and numbness of hands and feet. T.

Muscular weakness. T.

Aching from lower back down legs to ankles before menses. P-40.

Aching in right leg before menses. P-40.

Itching papules inner side right knee which form scabs after scratching. P-42.

Tiny, hard cores of epithelium exfoliate from surface of lower extremities. P-42.

Red papule on inner side of left knee having a pricking-out ward sensation, as if there was a piece of steel in it. It seemed to scratch the other leg when walking. Prover dug out a hard core which left a hole filled with serum. Took a long time to heal. P-42.

Cramps in calves of both legs, worse on right side, worse from 6 to 12 p.m., worse standing, worse walking, better from rubbing.P-42.

NERVES.

Paraesthesias. T.

Numbness and tingling of hands and feet. T.

General malaise and lassitude. T.

Easy fatigue. T.

TEMPERATURE and WEATHER.

Amelioration from hot applications. P-42.

Amelioration in open air. P-40.

FEVER.

Hyperpyrexia. T.

Hypopyrexia.T.

Sweating. T.

SKIN.

Urticaria. T.

Morbiliform eruptions. T.

Eruptions on exposure to sunlight. T.

Erythema multiform. T.

Jaundice. T.

Skin of lower extremities sensitive. T.

Sore, red pimples. P-40.

Sores with soft, yellow scabs, exuding bloody moisture. P-40.

Yellow pimples. P-40.

Scabby sore, burning and smarting, better from hot applications and when discharging. P-40.

Sore, red pimple behind angle of left jaw which appears during menses and after taking cold, and leaves a brown spot when healed. P-40.

Red, itching, macular eruptions. P-42.

Itching better from bathing in hot water. P-42.

Itching after scratching, burning. P-42.

Sore, papular eruptions, worse from touch. P-42.

Papules smart and burn, better when discharging. P-42.

Red papule on inner side of left knee having a pricking -outward sensation as if there was a piece of steel in it. P-42.

Papules changing to pustules, are sore, smart and burn, worse from touch, better when discharging. P-42.

OTHER MANIFESTATIONS.

Agranulocytosis. T.

Leucopenia. T.

Hemolytic anemia. T.

Lowering of the blood-plasma carbon dioxide-combining power. T.

Sulfhemoglobinemia and methemoglobinemia. T.

Acidosis. T.

Toxemia, resembling that of ethyl alcohol. T.

Severe toxemia with fever and rapid pulse. T.

Optic neuritis. T.

Allan D. Sutherland