Charles F. McKhann

Intracellular fluid loss in diarrheal disease

Summary Estimations of the extent and source of losses of body fluid by infants in an advanced stage of diarrheal disease were obtained from measurements of the excretion of sodium, potassium and nitrogen in the urine and stools. It was found that intracellular fluid is excreted in both urine and stools to an extent much greater than can be accounted for by release of water due to destruction of protoplasm. The additional water is regarded as withdrawn from tissue cells. The total quantity of withdrawn intracellular water was found to be larger than the loss of interstitial water. According to the findings in this study a loss of intracellular fluid, in addition to a loss of extracellular fluid, must be recognized in the process of dehydration produced by diarrheal disease.

The use of a blood coagulant extract from the human placenta in the treatment of hemophilia

Summary Tissue protein extracts prepared from the human placenta have been found to have the same type of effect in the control of local hemorrhage as has been reported from the use of animal tissue extracts. However, a striking difference has been observed in the results with this extract and those reported from the use of animal tissue preparations in the treatment of patients with hemophilia. Animal tissue extracts have shortened the coagulation time of the blood of patients with hemophilia for very brief periods, whereas human placental extracts have reduced the clotting time of both venous and capillary blood for periods varying from forty-eight hours to as long as nine days. Despite repeated slight trauma incident to active childhood, two children with hemophilia have been able to lead normal, active lives for periods of several months by the continued administration of this material at carefully regulated intervals. In the relatively small series of patients with hemophilia herein reported, the blood coagulant extract has been well tolerated by oral administration or by intramuscular injection. It must be emphasized that this blood coagulant extract is fatal when injected intravenously in small laboratory animals. Therefore, in using this material in patients with hemophilia, intravenous injection must be avoided as by this route unfortunate, if not fatal, results might ensue.

Factors Influencing the Effectiveness of Placental Extract in the Prevention and Modification of Measles.

Summary Placental extract can be prepared in large amounts and can be made available for the large scale prevention or modification of measles. Attempts to refine and concentrate the measles antibody have resulted in preparations of less potency than the extracts containing all of the globulins. However, the refined preparations can be passed through Berkefeld filters and may therefore be deemed safer to use. The results in a series of 1,258 cases demonstrate that the refined extracts, although less active than the crude preparations, are still effective in the prevention or modification of measles. However, this number of tests is inadequate to permit the determination of the best fraction of the extract to use and the dosage required in children of various ages and at various stages of the incubation period of the disease. The scarlet fever and diphtheria antibodies in placental extract appear to be almost entirely in the pseudoglobulin fraction, whereas the measles and poliomyelitis antibodies appear to be distributed throughout several protein fractions. The tissue protein insoluble in acidified salt solution contains no diphtheria antitoxin but does contain the antibody neutralizing poliomyelitis virus. It has not been tested for activity against measles. Reactions following the injection of placental extract, although infrequent, appear to be due in some measure to the inclusion in the finished extract of variable amounts of a specific tissue protein. A method of preparation and administration of extract to eliminate reactions is at present under investigation.

The Effect of X-Ray on the Antigenicity of Donor Cells in Transplantation Immunity

Summary The x-ray sensitivity of normal histocompatibility antigens in mice was studied. Strong antigens associated with the H-2 locus were found to be resistant to as much as 12,800 r in vitro , in that mice inoculated with such heavily irradiated cells were immunized by them and gave second set responses to subsequent skin grafts. Weak antigens associated with H-1 and H-3 loci were effectively destroyed by as little as 400 r, failing to induce immunity after irradiation in vitro . The cells used to induce immunity were spleen cells and a methylcholanthrene-induced sarcoma. Possible biologic relationships between strong and weak transplantation antigens are discussed and a reason for their different sensitivities to irradiation suggested.

Immunity and susceptibility to disease in early infancy

Summary The immunity of the newborn infant to certain diseases is passive in character and is soon replaced by susceptibility more marked than that of older individuals. This great susceptibility may account for many of the unusual characteristics of disease in infancy and is dependent apparently on a deficiency in the capacity of the infant to produce antibodies. This deficiency requires that more intensive therapy be applied toward infectious disease in infancy wherever such therapy is available, e.g., as in serum treatment of pneumonia. Also the inadequate antibody response in early infancy should lead to delay in the active immunizations at least until the second half year of life when passive immunity derived from the mother has been lost and immunizability of the infant is rising.

Respiratory acidosis and alkalosis in children.

Summary Respiratory acidosis and alkalosis occur probably more frequently than isgenerally believed and should be considered in patients presenting derangements of the respiratory mechanism. Cases illustrating the two conditions are presented. The diagnoses of respiratory acidosis and alkalosis are dependent not only on determinations of total plasma carbon-dioxide content but also of plasma pH. Whereas, in metabolic acidosis there is a correlation between the decrease in plasma carbon-dioxide content or alkali reserve and degree of acidosis, in respiratory acidosis there may be a normal or an increased plasma carbondioxide content with a decrease in pH. An opposite reversal is present in respiratory alkalosis, where plasma carbon-dioxide content may be decreased or remain normal with plasma pH definitely elevated. The mechanism whereby these changes occur may be as is shown in Table I. With the respiratory system deranged, as is the case in respiratory acidosis or alkalosis, the burden of maintaining a normal plasma pH falls more heavily on the renal mechanism. Compensation for increased or decreased H.HCO3 is attempted by altering the B.HCO3 so as to maintain a 1:20 ratio and thus a plasma pH of 7.4. The increase or decrease of B.HCO3 seems to occur through an increase or decrease of the chloride excretion. However, compensation is usually not complete and an abnormal plasma pH persists. Efforts to increase the renal mechanism of compensation appear inadequate and it seems that the treatment of respiratory acidosis and alkalosis had best be directed toward the correction of the underlying pathology which is responsible for the derangement of the respiratory system.

Regional lymph node response to skin grafts between strains of mice differing by strong and weak histocompatibility genes

Summary A study was made of the weight increase of regional lymph nodes following skin homografts. Grafts were transferred between combinations of co-isogenic strains of mice differing by a strong histocompatibility gene at the H-2 locus, by a weak gene at the H-3 locus, or by both. In all cases, the onset of the node response was evident by seven days. The peak response in each combination came near the time of graft destruction: 20 days for H-3, and 10 days for H-2 and H-2:H-3. The relationship of these results to the mechanism of the longer survival of skin grafts between mice having only weak genetic differences is discussed. A possible use of the regional lymph node response to detect marginal or inapparent immunity is suggested.

Acrodynia: A note on the pathologic physiology

Summary The data herein reviewed support the suggestion that the manifestations of acrodynia are dependent upon a diffuse disorder of the central nervous system with associated involvement of the autonomic nervous system. The mechanism by which the symptoms and physical signs of acrodynia are produced is, in large measure, traceable to a diffuse stimulation of the autonomic nervous system with involvement and overactivity not only of the sympathetic but also of the parasympathetic divisions of this system.

The baby's diaper with suggestions for its improvement.

Summary Appraisal of diapering practices leads to the conclusion that the infants diaper presents an hygienic and a sanitation aspect as well as being the indispensable garment. Attempts have been made with considerable success to improve the diaper so that it will be hygienically adequate, sanitarily effective, and acceptabe as a garment. A diaper designed to collect urine and stool of the infant with minimum contamination of the babys body and of his bed and clothing has in clinical trials proved 95 per cent effective for these purposes, at the same time reducing incidence of intertrigo and diaper rash, and not being uncomfortable or unsightly. Whether it will reduce materially simple pyuria, a purpose for which it was designed, can be proved only by more extensive trials.