Sickle cell.

The initiation of newborn screening and its virtually universal implementation will eventually yield a population in which sickle cell disease has been identified and comprehensive care is provided for children. The situation with SCT is different; there will continue to be the identification of parents who have the potential for having a child with a sickle cell disease but because they will not be tested or counseled, there will continue to be a population of children with a sickle cell disease whose parents have not been enabled to make informed decisions that they believe are in their best interest relative to family planning. Also, we will continue to have a population of pregnant women with a fetus with sickle cell disease who will not be given an opportunity to decide whether they wish to continue or terminate the pregnancy. They all will give birth to a child with a lifetime of chronic illness with its associated psychological, social, and financial burdens for the individual and his or her parents. The failure to implement prenatal diagnosis is an abridgment of two fundamental rights: the right to know and the right to decide. In this case it is the right to know about the potential health status of their children if that is possible, and the right to decide about the actual health care status of their children if options are available.

Postbaccalaureate program at Wayne State University School of Medicine: a 30-year report.

In 1969, Wayne State University School of Medicine established the first postbaccalaureate program for medical students, with the focus on African American students whose applications to medical school had been rejected. The ten-month program was designed to improve students' scientific knowledge, academic skills, and personal adjustment and thereby ultimately to increase the number of African Americans enrolled in the school. The criteria included the quality of the student's high school, employment workload, parents' ability to assist financially, and several other factors. The school covered expenses, provided a living stipend, and guaranteed admission for students who attained a B average in the program. Consistent with the Bakke court decision, in 1979 the program eligibility was shifted to disadvantaged students irrespective of race or ethnicity; all other criteria remained unchanged. Until 1990 Wayne State University's program was the only one of its type. From 1969 to 1992, 214 African American students who could have graduated by 1997 had been admitted to the program: 192 (90%) of them attained a B average in the program and matriculated in the medical school, and 160 (83%) graduated. From 1978 (when the program was opened to all racial and ethnic groups) to 1992, 58 non-African American students who could have graduated by 1997 were been admitted to the program: 54 (93%) attained a B average and matriculated in the medical school, and 51 (94%) graduated. The program's success suggests that similar programs at more medical schools could have an immediate and substantial impact on the number of underrepresented-minority students who enter medical education and succeed.

Estimating rates of psychosocial problems in urban and poor children with sickle cell anemia.

The risk of adjustment problems increases when a child has a serious life-threatening illness. This article estimates the frequency of adjustment problems across multiple domains for children and adolescents with sickle cell anemia (SCA). Parents provided information on the social, emotional, academic, and family adjustment of 327 children with SCA who were being treated at a comprehensive sickle cell clinic serving a predominantly poor and urban population. More than 25 percent of these children had emotional adjustment problems in the form of internalizing symptoms such as anxiety and depression. In addition, at least one child in five had problems related to social functioning and academic performance. These impairments were related significantly to the frequency of serious pain episodes but not to absolute family income. No significant differences in the data were found based on family income. The data also showed that the disruptive effects of the illness were related to gender and age.

The relationship between fetal hemoglobin and disease severity in children with sickle cell anemia.

A study was conducted in a sample of 140 children with sickle cell anemia to evaluate the relationship between hematological variables (%HbF, %HbA2, %Hb, and mean cell volume) and disease severity. A patient's severity status was determined by whether he/she was hospitalized, had a transfusion, and/or had a pain crisis at 2 evaluation periods; the first was based on a patient's history taken at the initial assessment visit to the Wayne State Comprehensive Sickle Cell Center, and the second was based on a 1-3 year follow-up at the center. Fetal hemoglobin was a strong predictor of a patient's hospitalization and transfusion status. A decrease in %HbF of 4.76% (one SD of %HbF) was associated with a 3.58 fold (95% confidence interval, 1.18-7.28) greater odds of being hospitalized both prior to initial assessment and on follow-up, compared to not being hospitalized at either evaluation. Similarly, a decrease in %HbF of 4.76% was associated with a 5.56 fold (95% confidence interval, 1.67-18.96) greater odds of having a transfusion both prior to initial assessment and on follow-up compared to not having a transfusion at either evaluation. Patients who were both hospitalized and transfused at initial assessment and on follow-up (n = 12) had a mean %HbF of 7.59%, while patients who were not hospitalized or transfused at either evaluation (n = 19) had a mean %HbF of 13.61%. Fetal hemoglobin was not a significant predictor of pain crises in this sample of patients. None of the other hematological variables were significant predictors of disease severity in this study. The strong relationship between %HbF and disease severity identified in this study suggests that a single %HbF measurement may be useful in predicting important aspects of the clinical course of children with sickle cell anemia.

Peripheral blood erythroid progenitors from patients with sickle cell anemia: HPLC separation of hemoglobins and the effect of a HbF switching factor.

We describe the use of HPLC for the separation and quantitation of hemoglobin and globin chains. Utilization of this sensitive technique allows the analysis of hemoglobin and globin chains in the total accumulated and newly synthesized hemoglobin. Using this methodology, we have studied the effect of a previously described HbF factor in fetal calf serum on peripheral blood BFUe-derived erythroblasts from patients with sickle cell anemia. As in previous studies of peripheral blood BFUe-derived erythroblasts from hematologically normal adults, this HbF factor promoted the increased synthesis of HbF in the BFUe-derived erythroblasts from the sickle cell anemia patients.

Stability over time of hematological variables in 197 children with sickle cell anemia.

One hundred ninety-seven children with sickle cell anemia were followed for 4 years at the Wayne State Comprehensive Sickle Cell Center to evaluate the stability of the hematological variables (Hb, Hct, RBC count, MCV, %HbF and %HBA2) over time. The mean values of the hematological measurements taken during three separate 16-month intervals were used to represent an individual's values. The correlations of the hematological variables between intervals ranged from a low of 0.46 for %HBA2 to a high of 0.91 for %HbF. Correlations that spanned two intervals (an average of 32 months) were of the same magnitude as those that spanned only one interval (an average of 16 months), suggesting that there was no decrease in the degree of stability of these variables as the time between measurements increased. The stability of the correlations between variables within intervals, and the stability of the coefficients of the first two principal components of the six hematological variables over time suggested that the relationships among variables were also stable. In a recent report [Odenheimer et al, 1983], we used the values of the six hematological variables collected at an individual's first visit to the sickle cell center to identify four hematologically distinct subgroups of children. In the current report, we found that as many as 83% of the individuals remained in the same subgroup in at least two of the three follow-up intervals, suggesting that the factors that contributed to this classification were the result of stable, rather than transient phenomena.

Heterogeneity of sickle-cell anemia based on a profile of hematological variables.

Factors that influence the heterogeneity of the disease expression of sickle-cell anemia are not well understood. This study examines the ability of a profile of six hematological variables (HB, HCT, RBC, %Hb F, MCV, and %HBA2) to predict the severity of disease measured on 225 patients ranging from 0.2 to 18 years of age. Four subgroups of patients were identified separately in each sex using cluster analysis techniques. In each sex, mean hemoglobin concentration and percent Hb F increased across the four clusters from 7 to 10 gm/dl and from 7% to 16%, respectively. Mean cell volumes were approximately 90, 80, 90, and 75 in groups 1, 2, 3, and 4, respectively; thus MCV did not increase in an orderly progression along with HB and %Hb F. We studied the distribution of four anthropometric, five physical examination, and seven clinical measures of disease severity among clusters. In each sex, subgroups differed significantly (P less than .05) for percent ever hospitalized for sickle-cell anemia, percent ever transfused, and percent with bone-age delays greater than 1 year. In addition, male clusters differed significantly for percent ever having had pneumonia, priapism, or dactylitis, and females differed significantly for height and weight. %Hb F and its inverse relationship with %HBA2 was more highly associated with the measures of severity than the degree of anemia or MCV. This study establishes the utility of a vector of hematological variables as a predictor of heterogeneity of measures of clinical manifestations among young patients with sickle-cell anemia. The role of alpha-thalassemia and genetic factors that affect Hb F levels were considered as possible explanations for the observed heterogeneity.

Sickle cell trait counseling-evaluation of counselors and counselees.

In this study, information about both counselee and counselor performance was obtained from taped recordings of 193 structured counseling sessions with persons diagnosed as having sickle cell trait. The data provide evidence that: (1) lay persons can understand essential sickle cell information; (2) trained lay persons using a structured format can transmit successfully sickle cell information; (3) only education and age, among counselee characteristics studies, were related to successful learning; (4) the evaluation of information transfer in counseling programs cannot be limited to counselees' comprehension but must also consider other variables such as counselor performance and curriculum content; (5) a reduction in negative feelings associated with a diagnosis of sickle cell trait is an immediate effect of counseling; and (6) audio-taping of counseling sessions is client acceptable and useful for evaluation, quality control, and counselor training.

Screening for psychosocial problems in health settings.

Providing comprehensive care requires identifying the total range of social, psychological, and medical needs that patients present to their health care providers. This study compares two approaches used to screen people for psychosocial problems in a hospital clinic. Findings suggest that a method in which clients identify their own problems yields different results from an alternative method in which professionals identify problem areas.

Incidence of cholelithiasis in sickle cell anemia using the ultrasonic gray-scale technique.

Gray-scale ultrasound examination of the gallbladder was successfully performed in 226 patients with sickle cell hemoglobinopathy from 2 to 18 years of age. Sixty-three (27%) demonstrated the presence of gallstones; 14 additional patients had "sludge." The incidence of gallstones increased significantly with age, from 12% in the 2- to 4-year age group to 42% in the 15- to 18-year-old group. The proportion of females with gallstones increased significantly in adolescence. Patients with gallstones had higher mean bilirubin levels, but their mean hemoglobin values and reticulocyte counts were not significantly different from those in patients without gallstones. Ultrasound examination of the gallbladder is a simple, noninvasive technique for evaluating the biliary system. The incidence of gallstones in patients below the age of 10 is higher than expected and raises management questions that must be resolved.

The effect of dietary sodium in infancy on blood pressure and related factors. Studies of infants fed salted and unsalted diets for five months at eight months and eight years of age.

The results of animal and epidemiological studies suggest commercially salted infant foods may predipose infants to hypertension. Testing this hypothesis, two groups of black male infants were fed identical foods with and without added salts for 5 months starting at 3 months of age. These diets, which provided 1.93+/-0.10 and 9.25+/-0.05 mEq Na/100 kcal, did not result in a significant difference in blood pressure at 8 months or 8 years of age. Blood pressure was significantly correlated with weight factors, particularly at 8 years, but not with Na intake, Na or Na/K excretion or plasma renin at 8 months. Significantly increased sodium and potassium excretion was noted on the salted diet and significantly increased aldosterone excretion was noted on the unsalted diet. A 6% expansion in extra-cellular fluid volume for the high sodium group was statistically significant but was not correlated with blood pressure or urine volume and did not result in edema or increased weight. There was no indication that the salted foods imprinted a preference for salt at 8 years. It was concluded that a salt intake representing the 99th percentile of sodium intake by U.S. infants in 1969 had no hypertensive effect in infancy or at 8 years of age. Nor did it imprint a preference for salt at 8 years.

Nitrogen balance and calorie efficiency in small-for-date dwarfism.

Accelerated weight gain was induced in eight infants, including two patients with dwarfing syndromes, who were small for their dates of birth and continued to be small after birth. The calorie cost of weight gain was higher than in control infants with linear growth failure due to undernutrition, but the degree of inefficiency did not seem to be of practical significance. Nitrogen retentions were appropriate for weight gain or better. Nitrogen retentions in excess of those expected on the basis of weight gain were seen in infants with small-for-date dwarfism and in controls when calorie intakes were low. The ability to induce good nitrogen retentions is thus no reflection of linear growth potential.