Biomedical subjects
J A Stockman
Publications and source records attributed to J A Stockman.
Resident, faculty, and residency program development. An integrated approach through annual retreats.
Retreats during residency training have evolved as an escape from the daily routine. Recognizing that the retreat format could also be used as a foundation for program design and personal development, we have designed annual retreats for each of the 3 years of pediatric residency training. The sessions vary in length and agenda, but serve as the basis for an ongoing effort fostering growth and maturation of the department and its component participants. The effectiveness of the program (and the morale of the residents) is greatly influenced by this program.
Transfusion medicine: the problem of HIV infection.
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Effects of intravascular, intrauterine transfusion on prenatal and postnatal hemolysis and erythropoiesis in severe fetal isoimmunization.
In an investigation of the effects of intrauterine, intravascular transfusions (IUT) on fetal and neonatal hemolysis and erythropoiesis, 12 fetuses who received IUT for treatment of severe isoimmunization had serial measurements of hemoglobin concentration, Kleihauer-Betke stains to detect fetal hemoglobin-containing erythrocytes, and determination of plasma erythropoietin (EPO) concentration before each IUT, at birth, and postnatally. Reticulocyte counts and sensitizing antibody titers were measured in five fetuses. Mean values before the first IUT, before the final IUT, and at birth were as follows: hemoglobin level, 6.1, 9.1, and 11.3 gm/dl; reticulocyte count, 22.7%, 0.5%, and 0.9%; fetal hemoglobin-containing erythrocytes, 100%, 1.6%, and 1.5%; and EPO level, 12, 56, and 756 mU/ml, respectively. Only one neonate required exchange transfusion. In the first month postnatally, all infants had a profound anemia. All but one infant required simple blood transfusions postnatally. Before the first postnatal transfusion, mean hemoglobin concentration was 6.2 gm/dl, mean reticulocyte count was 0.8%, mean erythropoietin concentration was 23 mU/ml, and the sensitizing antibody titer remained markedly elevated. Except for the surge of EPO at birth, EPO levels did not rise prenatally or postnatally unless marked anemia (hemoglobin level less than 5 gm/dl) occurred. These observations suggest that the intrauterine and postnatal anemia in fetuses who receive IUTs may be explained both by hemolysis of newly formed erythrocytes by circulating antibody, which typically persisted for more than a month after birth, and by suppressed erythropoiesis.
Regulation of working hours for pediatric residents.
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Effect of iron deficiency on tissue oxygen delivery in cyanotic congenital heart disease.
To test the hypothesis that tissue oxygen delivery would be affected by diminished oxygen stores in cyanotic congenital heart disease, serum ferritin, transferrin saturation, hemoglobin, red cell mean corpuscular volume (MCV), red cell 2,3-diphosphoglycerate (DPG), P50, blood gases, oxygen saturations and systemic oxygen transport were measured in 29 hypoxemic infants and children. For the group, aortic saturation was 81 +/- 9%, PaO2 was 50 +/- 12 mm Hg, hemoglobin 16.2 +/- 2.1 gm/dl and systemic oxygen transport 620 +/- 145 ml/min/m2. P50 was increased above normal values (28.8 +/- 2.3 vs 26.6 +/- 1.1 mm Hg, p less than 0.01), and DPG was 2.35 +/- 0.54 mumol/ml, at the upper limits of normal for this assay. Iron deficiency was present in 8. When patients with P50 greater than or equal to 30 mm Hg and P50 less than 30 mm Hg were compared, iron stores were diminished in the high P50 group: [serum ferritin (19 +/- 8 vs 53 +/- 48 ng/ml, p = 0.0006), transferrin saturation (11 +/- 6 vs 23 +/- 11%, p = 0.003) and MCV (79 +/- 8 vs 86 +/- 4 fl, p = 0.05)]. Hemoglobin, aortic oxygen saturation, PaO2 and systemic oxygen transport were similar in both groups. In children with iron sufficiency, 15 of 21 had MCV greater than 90th percentile for age and sex (p less than 0.001 versus expected distribution). Also, MCV greater than 90th percentile for age and sex had a positive predictive value of 0.88 for iron sufficiency. This study demonstrates that diminished iron stores in cyanotic congenital heart disease are associated with a more right-shifted oxyhemoglobin dissociation curve (increased P50).(ABSTRACT TRUNCATED AT 250 WORDS)
Erythropoietin in cyanotic heart disease.
We hypothesized that children with cyanotic congenital heart disease and moderate hypoxemia, as a result of erythrocytosis, and adequate iron stores would have low serum erythropoietin titers, low tissue oxygen delivery, and normal red cell 2,3-diphosphoglycerate (DPG) concentrations. We assessed hemoglobin levels, aortic oxygen saturation, iron stores, red cell 2,3-DPG, oxygen consumption, and systemic O2 transport in 19 hypoxemic patients, aged 3 months to 8 years. Low erythropoietin titers (less than 30 mU/dl) were found in 14 patients. Patients with high erythropoietin titers had lower Pao2 (36 +/- 7 vs 49 +/- 7 mm Hg, p less than 0.01), lower aortic saturation (68 +/- 12 vs 81 +/- 9%, p less than 0.01), and higher red cell 2,3-DPG (2.47 +/- 0.34 vs 3.23 +/- 0.73 mumol/ml, p less than 0.01). Aortic oxygen saturation higher than 80% was associated with a low erythropoietin titer and a hemoglobin level below that associated with hyperviscosity. The relationship between aortic oxygen saturation and hemoglobin concentration was strong (r = 0.77). These data suggest that for children less than 8 years of age, adequate compensation for moderate hypoxemia can occur with moderate increases in hemoglobin levels.
Erythropoietin: off again, on again.
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Practice-based research: opportunities and obstacles.
Renewed interest in practice-based research reflects growing realization of the limitations of research from a hospital perspective. Practice-based pediatric research promises to broaden the range and severity of conditions commonly studied, to enhance the study of the natural history of disease and of normal development, to provide normal controls and standards, and to facilitate recruitment of adequate sample sizes. Cohort, incidence, and health services research will be promoted by the development of patients registries. The Chicago area Pediatric Practice Research Group is a research consortium of 81 practitioners in 27 office practices. Formed in 1984, it receives logistic and financial support from Children's Memorial Hospital, with which it is affiliated. The Pediatric Practice Research Group has undertaken six studies, most with outside funding. During these studies, some unifying characteristics of practice-based research have emerged. These include the need to tailor study protocols to individual practice characteristics and routines and the critical role of office staff in the conduct of research. Features can be identified that make specific studies more or less intrusive into office functioning. It has proved feasible to obtain data of high quality and reproducibility despite geographically scattered data collection sites. This review of Pediatric Practice Research Group activities and experience is intended to open an exchange of ideas with others interested in practice-based research.
Iron deficiency anemia: have we come far enough?
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Anemia of prematurity. Current concepts in the issue of when to transfuse.
At no other time of life is the decision to transfuse potentially as difficult as in the newborn period. Superimposed upon complex "physiologic" changes in the ability to deliver and release oxygen are varying requirements among infants in terms of oxygen need. These are compounded by changes brought about as a direct consequence of frequent phlebotomy in the most ill of preterm infants. Despite the confusion overlying many of the changes occurring at this time of life, certain principles can be applied. Unlike that of the adult, an infant's ability to make oxygen available in response to a specific demand is almost as dependent upon the modifiers of oxygen uptake and release by hemoglobin as upon the hemoglobin concentration itself. These modifiers are constantly changing, sometimes in a predictable fashion, sometimes not. As discussed, some attention to the status of a particular infant's capability in providing oxygen relative to need will assist in the decision when to transfuse. If specific parameters of these assessments can not be determined, it may be necessary to proceed with transfusion based on the clinical presentation of an infant. With regard to the above, any infant sufficiently ill to require frequent blood sampling should have such blood losses replaced, certainly before ten percent of blood volume has been exceeded. This is particularly true in infants who are unable to maintain adequate arterial oxygen tensions with or without the use of supplemental inspired oxygen. At several weeks of age, when the clinical status of a preterm infant may have stabilized, transfusion may or may not be needed during the nadir of the anemia of prematurity. Infants who had been previously transfused or who had earlier received frequent simple transfusions should be able to tolerate lower levels of hemoglobin. Infants without compromised cardiopulmonary function and in whom no unusual metabolic needs exist are unlikely to be aided by transfusions when the hemoglobin concentration is greater than 10 to 11 g/dl. At lower levels of hemoglobin, simple calculations of "available oxygen" may be helpful when it is difficult to determine whether clinical signs and symptoms of anemia exist. Such signs and symptoms may include poor feeding, dyspnea, tachycardia, tachypnea, diminished activity, and pallor. Apnea has not unequivocably been shown to improve following transfusion. Clearly, our current concepts regarding indications for transfusion, even when based upon known principles of physiology, still represent an art form that is less than completely scientific.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibodies to human T-cell lymphotropic virus-I membrane antigens and inverted T4/T8 ratios in hemophiliacs.
Antibodies to the membrane antigens of human T-cell lymphotropic virus-I (anti-HTLV-MA) have been detected in patients with the acquired immune deficiency syndrome (AIDS) and in patients with hemophilia. The authors examined sera from 71 AIDS patients and 46 hemophiliac children for the presence of anti-HTLV-MA using an indirect membrane immunofluorescence assay with flow cytometry analysis. Thirty-seven of the 71 (52%) AIDS patients and 7 of the 46 (15%) hemophiliac patients had high titered anti-HTLV-MA, using a T-lymphoid cell line infected with the leukemia virus. None of the 78 control subjects had high titered antibody. All seven hemophiliac patients with elevated anti-HTLV-MA used Factor VIII concentrates, and all had inverted T-lymphocyte helper-suppressor (T4 [Leu-3]/T8 [Leu 2]) ratios. No correlations were found between inverted T4/T8 ratios and antibody to cytomegalovirus, Toxoplasma gondii, or hepatitis B. This work supports contentions that HTLV-like organisms cause AIDS and that these organisms are transmitted by blood products such as Factor VIII concentrate.
Iron absorption in the thalassemia syndromes and its inhibition by tea.
To determine the hemoglobin concentration at which iron absorption is minimal, five subjects with thalassemia major and one with thalassemia intermedia underwent a series of iron-absorption studies. The effect of tea as an inhibitor of non-heme iron absorption was also tested. Iron absorption increased as the hemoglobin concentration decreased, although iron absorption was much higher at any given hemoglobin level in the subject with thalassemia intermedia. In the subjects with thalassemia major, iron absorption averaged 10 per cent at hemoglobin concentrations between 9 and 10 and 2.7 per cent between 11 and 13 g per deciliter. The percentage of iron absorbed could be accurately predicted from the nucleated red-cell count (r = 0.91, P less than 0.001). Tea produced a 41 to 95 per cent inhibition of iron absorption. Since patients with thalassemia intermedia may absorb a large percentage of dietary iron, inhibitors of iron absorption, such as tea, may be useful in their management.
A prospective randomized study to determine the efficacy of steroids in treatment of croup.
We evaluated the use of dexamethasone in the management of acute laryngotracheobronchitis (croup). Thirty patients, ranging in age from eight to 60 months, were evaluated in a prospective, double-blind study. Patients received dexamethasone, 0.3 mg/kg at the time of admission and a similar dose 2 hours later, and were compared with a placebo group receiving saline. Sixteen patients received dexamethasone and 14 patients received the placebo. Severity of each group was scored by a standardized system. Patients receiving dexamethasone had a mean admission score of 8.46 points; patients receiving placebo, 8.14. Twenty-four hours after admission the patients in the treatment group had a mean score of 1.19 as contrasted with a score of 5.58 for the placebo group (P less than 0.01). We concluded that dexamethasone when administered in adequate dosage by an intramuscular route hastens the recovery of infants and children with acute uncomplicated croup.
L-Asparaginase-induced coagulopathy during therapy of acute lymphocytic leukemia.
L-Asparaginase-induced coagulation abnormalities were observed in all patients receivng this drug. All patients studied demonstrated low factor IX and fibrinogen levels and most (75%) had low levels of factor XI. Disturbances in other factors were much less frequent. Despite the presence of markedly abnormal coagulation studies, clinical bleeding was not observed.
Aspirin-induced hemolysis: the role of concomitant oxidant (H2O2) challenge.
Studies were conducted in an attempt to determine the hemolytic potential of acetylsalicylic acid (ASA) on normal intact red blood cells (RBCs). ASA (25 mg/100 ml) did not impair RBC G-6-PD, glutathione peroxidase or catalase activity, glutathione stability, or hexose monophosphate shunt activity. Hemolysis was not observed after incubation with ASA alone but was quickly noted after exposure to ASA (25 mg/100 ml) and H2O2 (1.2%). Hemolysis did not occur with H2O2 alone but was directly proportional to the ASA concentration. Hemolysis was preceded by peroxidation of membrane lipid and was inhibited by the presence of the antioxidant, thymol. With ASA and H2O2 a marked reduction in membrane phosphatidyl ethanolamine occurred with oxidation of 20:4 and 22:6 fatty acids. No effect on phospholipids or fatty acids occurred with either ASA or H2O2 alone. Salicylic acid, singly or with H2O2, does not exhibit these effects.
Physiological anaemia of infancy and the anaemia of prematurity.
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Consumptive coagulopathy. A complication of therapy of solid tumors in childhood.
The association of consumptive coagulopathy and malignancy is thought to be rare in pediatrics. In one patient with Ewing's sarcoma and in two with rhabdomyosarcoma consumptive coagulopathy developed in the presence of either diffuse metastatic disease or an extensive primary tumor. The coagulopathy was a major clinical problem, developing within five days of the onset of chemotherapy. Resolution coincided with the clinical response of the tumor.