Irving J. Wolman

TRANSFUSION THERAPY IN COOLEY'S ANEMIA: GROWTH AND HEALTH AS RELATED TO LONG-RANGE HEMOGLOBIN LEVELS. A PROGRESS REPORT.

What are the long-range consequences of keeping children with Cooley’s anemia a t one or another level of blood hemoglobin over long periods of time? Expressed another way, is the growth and health of such children related to their long-range hemoglobin levels ? This important question is difficult to answer from comparisons of a few cases treated by dissimilar schedules. Patients differ widely in so many ways in their genetic backgrounds, in the severity and expressivity of their disease, in their intercurrent illnesses and dietary and other environmental influences, and in their medical care, transfusion schedules, and responsiveness to therapy. Factors which complicate the comparative appraisal of different treatment programs include such variables as: (1) The time interval after birth before the condition is recognized and transfusion therapy is begun. This is important because infancy is the period of most rapid growth. Young patients may go for months or even years a t slowly falling hemoglobin levels with no relief to the bone marrow from transfusions and with all compensatory mechanisms operating a t maximal capacity. (2) The duration and degree of chronic hypoxia of the blood and tissues while the child is growing up, (3) The intensity and effectiveness of the compensatory physiologic responses such as cardiac output and bone marrow hyperplasia. (4) The inevitably associated great accumulation of iron in the body, coming from enhanced absorption through the bowel wall as well as from obsolescence of transfused red cells. (6) The poorly understood hemopoietic and hemodestructive activities of the spleen, plus the fact that many of the cases undergo splenectomy a t inconstant ages. (6) The derangements of function of such vital organs as the liver and heart and enzyme systems everywhere, and the secondary back-action of these derangements upon the body as a whole.

SOME CLINICAL FEATURES OF COOLEY'S ANEMIA PATIENTS AS RELATED TO TRANSFUSION SCHEDULES

The clinical remarks presented in this paper are derived from a continuing study of patients with Cooky’s anemia (beta-thalassemia) being carried out principally in Philadelphia, Pennsylvania, U.S.A., and Ferrara, Italy. Many professional colleagues in both cities are collaborating in these activities. Comments will concern a few facets only: variability of the disease in relation to comparative studies; extramedullary hemopoiesis (EMH);* fetal hemoglobin levels; retardation in growth; prognosis with high hemoglobin regimens; and iron deposition and desferrioxamine (DeferaP, CIBA). T o maintain a high hemoglobin level (HH)* typically requires a transfusion of fresh-packed red cells in appropriate amounts every three weeks for smaller children and every two weeks for adolescents and young adults. Maintainance of a medium hemoglobin (MH)* level typically requires a transfusion every five to eight weeks with smaller children and every four to six weeks with older ones. A low hemoglobin (LH)* level is usually associated with single transfusions at infrequent and sporadic intervals.

The role of vincristine in the treatment of childhood acute leukemia

In a study of 117 patients under the age of 20 with acute leukemia, vincristine (VCR), at 2 mg. per square meter body surface per week, produced complete remissions in 55 per cent and partial remissions in 15 per cent. The drug also induced second remissions. Patients entering complete remission with VCR were randomly allocated to maintenance therapy with VCR or placebo. The median duration of remission was short: 9 weeks for VCR compared with 6 weeks for placebo. The probability of serious neurological toxicity computed according to the time of exposure to VCR, based on the supposition that VCR was not used for maintenance therapy, indicated that the minimal theoretical risk of toxicity for the highest complete remission rate occurred at 4 weeks (38 per cent remissions with 5 per cent toxicity). At 6 weeks, the corresponding probabilities were 54 and 16 per cent.

Clinical Use of Cold Precipitated Antihemophilic Globulin (Factor VIII, CPAG)

A fibrinogen fraction separated from fresh frozen plasma by slow thawing at 2 C contains Factor VIII activity. The administration of this material to six patients with hemophilia A resulted in partial to complete correction of their clotting defect. Clinical hemostasis was associated with these infusions. Normal or higher than normal levels of Factor VIII were observed in one patient given this material in connection with surgery. Side effects did not occur during or after the administration of the fraction. The preparation of this material is simple and can be carried out as a routine procedure in blood banks processing large amounts of fresh frozen plasma.

Plateletpheresis and Plasmapheresis In the Routine Operation of a Children's Hospital Blood Bank

* Director of the Blood Bank, and Associate Hematologist, The Children’s Hospital of Philadelphia; Assistant Professor of Pediatrics, University of Pennsylvania Medical School. t Fellow in Hematology, Children’s Hospital of Philadelphia. ‡ Hematologist, Director of Clinical Laboratories, Children’s Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania Medical School.

Soft curd homogenized milk in infant feeding

Summary Pasteurized milk homogenized by means of (a) the sonic homogenizer,(b) the low pressure homogenizer, and (c) the high pressure homogenizer in accordance with sound principles of milk technology has been compared with boiled pasteurized milk as a base for infant formulas, using both laboratory and clinical techniques of observation. Each of these milks containing added carbohydrate was fed unboiled and undiluted to over 200 infants for from two to twelve months. There was a low incidence of constipation, diarrhea, vomiting, and kindred gastrointestinal upsets in all groups, and the babies grew and thrived normally. In digestibility and safety the homogenized milks proved as satisfactory as the control boiled milk. Laboratory studies demonstrated that by use of holding pasteurizationtemperatures of from 150 to 160° F. for thirty minutes, the bacterial counts of homogenized milks can be kept at low levels, usually below 2,000 per milliliter, with resulting high sanitary quality and without the introduction of an objectionable heated flavor. The curd tension and related values fluctuated with the seasons andwere at different levels with each type of homogenized milk, but the changes and differences did not give rise to detectable clinical disturbances. In the light of this finding and related observations recorded in the literature, the suggestion is made that there exists a threshold or dividing zone which delimits readily digested or soft curd milks from less thoroughly processed milks or from plain pasteurized milk.

Chemotherapy of the leukemic transformation of lymphosarcoma.

The chemotherapy of leukemic transformation of lymphosarcoma has been studied in seventeen children. Complete hematologic remission was obtained in 88 per cent treated with 6-mercaptopurine and prednisone. Maintenance therapy with 6-mercaptopurine was employed and the median duration of remission was 21 weeks. These results are comparable to those obtained in a series of children with acute lymphocytic leukemia in which the remission rate was 82 per cent and median duration of remissoin was 33 weeks with the same therapy.

Some Prominent Developments in Childhood Nutrition: 1972

many poor people are able to give their families sufficient food for most of each month, but during the final week or half-week the children go hungry, and may cry themselves to sleep because of their hunger. Type 3. &dquo;When an individual is unable to acquire those foods which are most commonly used in the society and culture to which he belongs.... Poor people will not willingly accept foods labeled ’for the poor’ no matter

Problems in the Diagnosis and Management of Acute Leukemia in Childhood Comments Based on a Survey of 100 Recent Patients

The early recognition of leukemia rests on a heightened awareness of the possibility of this disease in children with obscure symptoms. Once suspected, confirmation of the diagnosis is not difficult. The natural history of the disease has altered considerably in the past ten years due, in large part, to the increased survival. Problems of infection and localized collections of leukemic cells are now of major importance when trying to support patients in relapse.The early recognition of leukemia rests on a heightened awareness of the possibility of this disease in children with obscure symptoms. Once suspected, confirmation of the diagnosis is not difficult. The natural history of the disease has altered considerably in the past ten years due, in large part, to the increased survival. Problems of infection and localized collections of leukemic cells are now of major importance when trying to support patients in relapse.

An evaluation of the curd-forming properties of milk mixtures used in infant and child feeding

Summary The curd-forming properties of milks and milk mixtures used in infant feeding have been studied, employing testing procedures which simulate intragastric conditions. The results confirm that heat treatment, dilution with water acidification and homogenization, if adequately employed, are effective methods of eliminating the tendency of unmodified cows milk to form large firm coagula in the stomach of the infant and child. Fever temperatures aggravate the tendency to “hard formation”. Apple syrup reduces this tendency a little; banana, more so; whereas corn starch derivatives exert no influence. Goats milk is not as often maintained, naturally soft curd but shows similar reaction as cows milk toward treatment with heat, dilution, and homogenization.