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A SUGGESTION OF THE THERAPEUTIC VALUE OF GLUCOSE BASED ON INVESTIGATION OF CARBOHYDRATE METABOLISM OF THE FEEBLEMINDED*
BY A. N. BRONFENBRENNER, Ph. D., M. D.,
PATHOLOGIST, LETCHWORTH VILLAGE, THIELLS, N. Y
About two years ago when we first undertook the study of the problem of mental deficiency from a laboratory standpoint, we did not have any idea what particular line of laboratory investigation was the most profitable to pursue, nor did we know what laboratory tests should be applied and could be applied to the kind of patients, who, presumably, were not cooperative, and therefore, hard to deal with. We could not find in the literature any reports of laboratory work done on mental defectives. Even the simplest routine tests had not been done on any large groups of defectives. Hence we did not even know what the normal standards of urinalysis, blood counts, blood chemistry, etc., for the physically-normal defectives were. Therefore, it was deemed advisable to accumulate data that would establish a foundation for further investigation.
Eventually we expect to report on various tests which have already been done often enough to establish standards for mental defectives. Meanwhile the nature of these data now on hand already creates advanced laboratory and clinical problems and even suggests some ideas which might be helpful in the management and treatment of our patients. It appeared advisable to make this preliminary communication which deals with a therapeutic suggestion, because we hope in this way to get constructive criticism and cooperation in the clinical checking of the suggestion. It is generally accepted that the resistance of mental defectives to the different infections is lower than that of normals. Even minor injuries without any apparent complication often do not heal as readily as they usually do in normals. And yet this retardation in the healing process is accompanied neither by any apparent signs of generalization nor by any especially marked local reaction, both of which if present would account for the delayed recovery.
During the cold season of the year in any group of patients in our institution there are a certain number cases with minor sores on their fingers or toes. The involved area is painful and tender and appears cyanotic, swollen and may, or may not be accompanied by a limited ulceration. If ulceration is present there is a scant mucopurulent or serous discharge. No matter what the treatment
* Publication Letchworth Village, N-28.
is, the inflammation develops slowly, temporarily subsides, then again increases, breaks down and closes again. Such sores last for two, three, or more months. Eventually, mostly with the oncoming of the warm season, the process heals up only to reappear the next cold season, on the same or another extremity.
The process of inflammation consists of a reaction of an organism to some sort of injury. There is no difference in the injuries that a mental defective is exposed to, as compared with the injuries that another human being may be exposed to. Therefore, the difference in the course of the inflammatory reaction apparently must depend upon the peculiarities of the reacting organism or in this instance upon the entire make-up of the defective. The whole make-up and general metabolism of a human being may be looked upon, to some extent at least, as respectively the static and dynamic phases of the same phenomenon. Therefore, it is the metabolic process of mental defectives that might afford the explanation for this retardation in the healing process.
General metabolism takes an essential part in any process, accompanied by disintegration of bodily cells. It is especially so when products of inflammation have to be absorbed and subsequently eliminated through the channels of the metabolic mechanism. An illustration of this is represented by the clinical course of lobar pneumonia in which practically the whole bloody, mucopurulent exudate is digested and absorbed from alveoles by the process of general metabolism. Therefore it is not surprising that we find in the urine for instance, an increase of some substances produced by an inflammatory disintegration.
One kind of products of disintegration of bodily cells is a part of urinary reducing substances that are often discussed under the name "urinary sugar." Our sugar test is based mostly on the phenomenon of reduction of copper sulphate by sugars and adjusted to show, so to say, pathological quantity of the sugar in urine. At the same time more sensitive adjustments of the test are devised for the purpose of estimating so-called "physiological” urinary sugar that can be shown in any specimen of any urine. These copper sulphate reagents react with glucose and closely related other simple sugars, so-called monosaccharids. The tests do not react with the more complex sugars, so-called polysaccharids. But these complex sugars are present in the urine as derivatives of food as well as products of disintegration of bodily cells. By boiling the urine with acid-by hydrolysis, to use the proper chemical term-these complex sugars are split into simple sugars that do
react to ordinary sugar tests. Therefore, estimating sugar in urine as it was collected, then hydrolysing the urine and repeating the sugar estimation, we practically always find an additional quantity of the reducing substances. In this paper we shall deal with this additional part of urinary reducing substances and we shall refer to it under the name post-hydrolysis reducing substances.
Post-hydrolysis reducing substances are caloricly valuable but difficult to assimilate. They are thrown out into the urine, generally speaking, because of the presence of an abundance of more easily assimilable sugars or because of a failure of the metabolic mechanism. The first situation we meet in mental normals, and it has been shown by Folin and others that the post-hydrolysis reducing substances of the urine are increased in quantity in the presence of a rich carbohydrate diet. With mental defectives the usual quantity of carbohydrates in the diet is apparently insufficient for their peculiar metabolic mechanism because when a considerable part of the carbohydrates of their customary high carbohydrate diet was substituted by a caloricly equivalent quantity of proteins, there was a grave loss in their body weight. At the same time the elimination of the post-hydrolysis reducing substances in the urine was increased. This is just the reverse of what happens with mental normals. These observations on defectives were discussed in detail at the Toronto meeting of the American Association for the Study of Mental Deficiency in our communication entitled "Glycuresis in Mental Defectives."
We inferred therefore, that mental defectives require a large quantity of carbohydrates for their nutritional standards to compensate for their impaired metabolism. Apparently the metabolic mechanism of defectives has to make an extreme effort to meet ordinary requirements.
Now what will happen if the metabolic mechanism of a defective is called upon to take care of an increased disintegration of bodily cells that comes with any inflammation? We must expect that the products of disintegration instead of being properly metabolized will be harbored within the tissues and thus retard the healing process shown in the urine as post-hydrolysis sugars. Therefore, we may infer that the administration of glucose which increases the glucose circulating within the metabolic channels must be of therapeutic value in the retarded inflammatory processes of mental defectives.
The conception just presented, I believe, is logically constructed, but the only way of proving it is the clinical check of this theoretical,
partly speculative idea of therapeutic value of glucose in cases of retarded healing of minor inflammatory processes. At the present time I have two cases to report.
Case I. R. J., 11-year-old boy with M. A., 2 years and 7 months. I. Q.5, a typical Mongolian idiot. On February 15, 1926, the patient was admitted to our hospital with a fractured ulna and made an uneventful recovery. While in the hospital the toes of the left foot became red, swollen, painful and tender. On March 10, the patient was put to bed. All sorts of local applications were used. The condition did not improve and finally the third toe became ulcerated. More than a month after the beginning of the condition, on March 18, the toe was lanced. No improvement followed. All this time the temperature was normal, general condition, disposition, appetite very good.
On June 1, 1926, our attention was called to the case and observation was started. The toe at the time was slightly swollen, cyanotic, with a small 1⁄2 cm in diameter ulceration over the tip involving nail area, and nail almost completely disappeared. X-ray of the toe done at the time reads, "Terminal phalanx of third toe gone." General health good. The patient had no complaints, and apparently felt quite well. The inflammation of the toe had lasted more than three months at this time.
No treatment was applied for 14 days. The toe was kept dressed in gauze with some vaseline on it to avoid sticking of the gauze to the ulcerated area. Hence we had an adequate control period. No change in the condition was noticed during this control period. Average of urinary post-hydrolysis reducing substances within this period was 142 mg. per 24 hours. On June 14, glucose, 50 gm., per day orally was ordered. On June 19, five days after glucose was ordered, daily note reads "Crust removed, perfect healing with prima intention. Nail is growing anew." Dressings were discontinued. Patient was ordered out of bed. Average of primary posthydrolysis reducing substances within this five-day period of accelerated healing-163 mg. per 24 hours, 21 mg. higher than during control period. This is just what is expected to happen when the general metabolism takes its proper part in evacuating the products of disintegration of the bodily cells accompanying the healing process.
After healing glucose administration was continued for seven days with the result that the urinary post-hydrolysis substances were decreased to the average of 114 mg., per 24 hours. Then followed seven days of further observation, the glucose had been
discontinued on June 27, with a still further decreasing quantity of post-hydrolysis sugars in urine--102 mg. per day.
On July 4, the patient was allowed to go home for a vacation with his parents. At the present time the patient has returned from his vacation and his toe has been in perfect condition all the time. (September 15.)
Summary of the case: Five days glucose treatment resulted in perfect healing of a minor inflammatory process that lasted for four months without any improvement in spite of all sort of local
Cass II. Will be reported briefly. L. F., 18-year-old girl with mental age of 7 years that makes her I. Q. 44. She was born as a premature 7 months baby, 11 days after mother's fall. No nervous or mental defects on either side of the family for three generations. The parents are first cousins, and patient's brother is in an ungraded class.
The patient is fairly developed, well nourished but has spastic paresis of both legs with Babinsky present on both feet.
On August 5, 1926, she was sent to the hospital on my service with Dr. Veith's note as follows: "On February, 1926, the patient complained of pain in the fourth toe of the right foot. The toe was painful, swollen, cyanotic for about three weeks and then broke down; scant discharge of pus but no definitely localized process. It took about six weeks to heal. Used salt and water, then alcohol dressing. After healing the toe stayed swollen and cyanotic for about one month and then became normal."
Patient's toe became swollen, cyanotic and painful again three weeks ago. In the hospital she underwent treatment as follows. No treatment for 12 days; no improvement. Then under 50 gr. glucose per day orally the inflammatory process subsided and healed within 10 days. During these 10 days the old nail of the toe came off and a new one appeared. The condition has not reappeared up to the present time which is about one month after healing.
The metabolic mechanism of mental defectives is impaired to some extent. Their impairment has been shown by their peculiar handling of certain substances which are derived from both food and disintegration of bodily cells and are the source for the afterhydrolysis fraction of urinary reducing substances. The high carbohydrate diet, resulting in an increased quantity of glucose circulating within the metabolic channels, appears to compensate