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Children with sickle cell anemia (HbSS) are at high risk for neurologically overt cerebral infarcts associated with stroke and neurologically silent cerebral infarcts correlated with neuropsychometric deficit. We used complete magnetic resonance imaging (MRI) histories from 266 HbSS children, aged 6 through 19 years, who were enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) to examine silent infarct prevalence, localization, recurrence, and progression. We report a baseline prevalence of 21.8%, marginally higher than previously reported due to improved imaging technologies. Although we observed no overall sex difference in prevalence, most lesions in girls occurred before age 6, whereas boys remained at risk until age 10. Silent infarcts were significantly smaller and less likely to be found in the frontal or parietal cortex than were infarcts associated with stroke. Children with silent infarct had an increased incidence of new stroke (1.03/100 patient-years) and new or more extensive silent infarct (7.06/100 patient-years) relative to stroke incidence among all children in our cohort (0.54/100 patient-years). Both events were substantially less frequent than the risk of stroke recurrence among children not provided chronic transfusion therapy. Although chronic transfusion is known to decrease occurrence of new silent infarcts and strokes in children with elevated cerebral arterial blood flow velocity, further study is required to determine its risk-benefit ratio in children with silent infarct and normal velocities. Until safe and effective preventive strategies against infarct recurrence are discovered, MRI studies are best reserved for children with neurologic symptoms, neuropsychometric deficits, or elevated cerebral artery velocities.

Objectives: Although hydroxyurea is effective in treating adults with sickle-cell anemia (SCA), there is concern that it may adversely affect growth in children. We report the growth characteristics of patients in the Phase I-II pediatric hydroxyurea trial (HUG-KIDS) before and during treatment at the maximum tolerated dose for one year. Study design: Children and adolescents with SCA (n = 68), aged 5 to 16 years at baseline, reached the maximum tolerated dose and had serial height, weight, and Tanner stage measurements. Data from the Cooperative Study of Sickle Cell Disease (CSSCD) were used for comparison. Mixed-effects models were used to compare serial measurements as a function of age and group. Results: In girls, there were no significant differences in height or weight among the pretreatment, on-treatment, and CSSCD groups. Compared with the CSSCD group, HUG-KIDS boys were heavier starting at age 9 years, and pretreatment HUG-KIDS boys were taller starting at age 7 years. The Tanner stage transitions took place at appropriate ages. Conclusions: Hydroxyurea treatment had no adverse effect on height or weight gain or pubertal development in school-aged children with SCA. (J Pediatr 2002;140:225-9)

In the phase I/II pediatric hydroxyurea safety trial (HUG-KIDS), school-aged children with sickle cell anemia receiving hydroxyurea at the maximally tolerated dose (MTD) had variable increases in the percentage of fetal hemoglobin (%HbF). To identify predictors of the HbF response to hydroxyurea therapy, baseline clinical and laboratory values (age, sex, hemoglobin concentration, %HbF, reticulocytes, white blood cell [WBC], platelets, and serum chemistries), as well as treatment variables (number of toxicities, noncompliance, MTD dose, and MTD blood counts) were analyzed in 53 HUG-KIDS children who achieved MTD. Baseline %HbF values (P = .001), baseline hemoglobin concentration (P = .01), MTD dose (P = .02), and compliance (P = .02) were significantly associated with a higher %HbF at MTD; in contrast, age, sex, number of toxicities, and other baseline hematologic parameters were not. After adjusting for variations in baseline %HbF, the baseline reticulocyte count (P = .05) and baseline WBC count (P = .05) were also significantly associated with a higher %HbF at MTD. Hydroxyurea-induced increases in the hemoglobin concentration and mean corpuscular volume (both higher absolute values at MTD and larger positive changes from baseline values), as well as hydroxyurea-induced decreases in reticulocytes and WBC count, were significantly associated with a higher %HbF at MTD. These data suggest that selected baseline laboratory parameters, a higher MTD dose with attention to compliance, and greater therapy-related changes in blood counts may predict the HbF response to hydroxyurea therapy for children with sickle cell anemia. The HbF response to hydroxyurea is variable and complex, however, and even children with low baseline %HbF values can develop substantial increases in %HbF at MTD.

Objective: To determine whether children with homozygous sickle cell anemia (SCD) who have silent infarcts on magnetic resonance imaging (MRI) of the brain are at increased risk for overt stroke. Methods: We selected patients with homozygous SCD who (1) enrolled in the Cooperative Study of Sickle Cell Disease (CSSCD) before age 6 months, (2) had at least 1 study-mandated brain MRI at age 6 years or older, and (3) had no overt stroke before a first MRI. MRI results and clinical and laboratory parameters were tested as predictors of stroke. Results: Among 248 eligible patients, mean age at first MRI was 8.3 ± 1.9 years, and mean follow-up after baseline MRI was 5.2 ± 2.2 years. Five (8.1%) of 62 patients with silent infarct had strokes compared with 1 (0.5%) of 186 patients without prior silent infarct; incidence per 100 patient-years of follow-up was increased 14-fold (1.45 per 100 patient-years vs 0.11 per 100 patient-years, P = .006). Of several clinical and laboratory parameters examined, silent infarct was the strongest independent predictor of stroke (hazard ratio=7.2, P = .027). Conclusions: Silent infarct identified at age 6 years or older is associated with increased stroke risk. (J Pediatr 2001;139:385-90)

Objectives: Glomerular disease and renal failure cause substantial morbidity for patients with sickle cell disease (SCD). Proteinuria is an early manifestation of sickle nephropathy, but the prevalence of proteinuria and its clinical correlations in children with SCD are unknown. Study design: Data were collected prospectively on children with SCD for 10 years including physical measurements, laboratory test results, and clinical complications. Persistent proteinuria was defined as ≥1 + protein on urinalysis for at least 6 months. The glomerular filtration rate was estimated with serum creatinine concentration and height. Proteinuria was correlated with other variables by χ 2 analysis. Results: Proteinuria occurred in 20 of 442 pediatric patients including 15 (6.2%) with sickle cell anemia. Proteinuria increased with age, affecting 12% of older teenagers with sickle cell anemia. Proteinuria was significantly associated with lower hemoglobin concentration, higher mean corpuscular volume, and higher leukocyte count. For children of some ages, proteinuria was associated with complications including stroke, acute chest syndrome, cholelithiasis, and hospitalizations. Glomerular filtration rate hyperfiltration occurred early in life, followed by normalization. Conclusions: Sickle nephropathy, manifested as persistent proteinuria, begins early in life, occurs in all forms of SCD, and is associated with severity of disease. Early detection of proteinuria may allow therapy to prevent progressive renal insufficiency.

Background. Silent infarcts have been reported in 17% of young patients with sickle cell disease and are associated with impaired performance on standardized psychometric tests. Risk factors for the development of these lesions have not been identified. Methods. Investigators in the Cooperative Study of Sickle Cell Disease performed a brain magnetic resonance imaging scan on sickle cell anemia patients age 5.9 years and older who had been followed according to the protocols of the Cooperative Study since birth. Individuals with a known history of cerebrovascular accident were excluded from this analysis. Patients with and without silent infarctions were compared with regard to clinical and laboratory parameters. Results. The study sample included 42 patients (18.3%) with silent infarcts. Patients who had silent infarcts were significantly more likely to have a clinical history of seizure and a lower painful event rate. Lower hemoglobin level, increased leukocyte count, elevated pocked red blood cell count, and SEN βS globin gene haplotype were associated also with the presence of silent infarcts. There was no relationship between silent infarcts and platelet count, fetal hemoglobin level, reticulocyte percentage, serum aspartate aminotransferase level, total bilirubin concentration, blood pressure, growth parameters, or presence of α-thalassemia. A multivariate model for silent infarction identified the following as risk factors: low pain event rate, history of seizure, leukocyte count ≥11.8 × 109/L, and the SEN βS globin gene haplotype. Conclusions. Patients with risk factors for silent infarcts should be evaluated for cerebrovascular disease. If evidence of infarction is found, consideration must be given to therapeutic intervention. At present, the appropriate treatment has not been determined.

Objectives: This study has three interrelated objectives: (1) to track the adjustment of children and adolescents with sickle cell disease (SCD) or cystic fibrosis (CF) and their mothers through a third assessment point 2 years after the initial assessment; (2) to determine whether the adaptational processes of the transactional stress and coping model associated with adjustment at the initial assessment continue to be associated with adjustment 2 years later; and (3) to determine whether the pattern of association of adaptational processes with adjustments differs by illness subgroup. Methods: The study samples included 59 children with CF and 50 children with SCD and their mothers. Measures were obtained on maternal adjustment and appraisals of daily and illness stress, coping methods, and family functioning. Child measures included child-reported and mother-reported child adjustment and child perceptions of self-worth and health locus of control and pain coping methods. Results: Consistency in adjustment classification was only 31–32% for child self-report, 66% for mother-reported child behavior problems, and 56–77% for mother self-reported adjustment for the CF and SCD groups, respectively. Support was provided for the association of adaptational processes with maternal adjustment and with the adjustment of children with SCD but not for children with CF. Conclusion: The stability of adjustment has implications for prevention and treatment intervention and subsequent research steps. Intervention efforts should be focused on the relatively small subgroups of children with chronic illnesses and their mothers with consistently poor adjustment.

Background/Purpose : Surgery in patients with sickle hemoglobinopathies can be problematic because of the potential for sickling events in the perioperative and postoperative period. The authors and others have previously reported successful surgical outcomes using an aggressive erythrocyte transfusion regimen, designed to alleviate anemia and to reduce the percentage of sickle hemoglobin to below 30%. Recently, a randomized trial compared this aggressive regimen with a more conservative transfusion regimen and found no differences in perioperative complications. The incidence of complications, however, was very high in each group (31% to 35%). Methods : The authors therefore analyzed retrospectively their surgical experience in children with sickle hemoglobinopathies over the past 10 years to determine the efficacy of an aggressive transfusion regimen and skilled perioperative care in their patient population. Results : A total of 130 surgical procedures were performed on 92 children including 54 cholecystectomies (42%), 23 splenectomies (18%), 12 ENT procedures (9%), 11 central line placements and removals (8%), 7 herniorrhaphies (5%), 7 appendectomies (5%), and 16 miscellaneous operations (13%). The mean age of the children was 10 years (range, 1 to 22 years), and the mean weight was 32.1 kg (range, 9.9 to 76.8 kg). The average hemoglobin (mean ± 1 SD) at the time of surgery was 11.2 ± 1.3 g/dL, and the average percent hemoglobin S was 21 ± 11%. Conclusions : Relatively few transfusions were required to achieve these endpoints, and the complications resulting from transfusions were minimal. Similarly, the number of perioperative and postoperative events was very low.

PURPOSE To evaluate the consequences of prolonged prophylactic penicillin use on the rates of nasopharyngeal colonization with Streptococcus pneumoniae and the prevalence of resistant pneumococcal strains in children with sickle cell anemia. METHODS Nasopharyngeal specimens were obtained from children with sickle cell anemia (Hb SS or Hb S beta degrees thalassemia) at 10 teaching hospitals throughout the United States. These patients were participating in a prospective, randomized, placebo-controlled trial in which they were prescribed prophylactic penicillin before their fifth birthday and were randomized to prophylactic penicillin or placebo after their fifth birthday (PROPS II). The specimens were cultured for S. pneumoniae, and isolates were analyzed for antimicrobial susceptibility to nine commonly prescribed antimicrobial agents. RESULTS Of the 226 patients observed, an average of 8.4 specimens were collected per patient. From 1,896 individual culture specimens, 5.5% of the specimens were positive for S. pneumoniae; 27% of patients had at least one positive culture. Nine percent of the study patients had at least one isolate of penicillin intermediate or resistant pneumococci. There was no significant difference in the percent of positive cultures for S. pneumoniae in those patients given penicillin prophylaxis after 5 years of age (4.1%) compared with those patients given placebo after 5 years of age (6.4%). Likewise, there was no significant difference (p = 0.298) in the percent of patients with at least one positive culture for S. pneumoniae in the group given prophylactic penicillin after 5 years of age (21.8%) compared with the group given placebo after 5 years of age (28.3%). There was no difference between the penicillin and placebo groups in the proportion of patients with penicillin intermediate or resistant pneumococci, but there was a trend toward increased carriage of multiply drug-resistant pneumococci in children > 5 years of age receiving prophylactic penicillin compared to children > 5 years of age receiving placebo. The increased colonization rate with multiply drug-resistant organisms of children > 5 years of age receiving penicillin prophylaxis is not statistically significant. CONCLUSIONS The potential for continued penicillin prophylaxis to contribute to the development of multiply resistant pneumococci should be considered before continuing penicillin prophylaxis in children with sickle cell anemia who are older than 5 years of age. Added to the published data from PROPS II, which demonstrated no apparent advantage to continue prophylaxis, the data support the conclusion that, for children with no history of invasive pneumococcal disease, consideration should be given to discontinue prophylactic penicillin after their fifth birthday.

Studies have found that coping strategies are significant predictors of pain report, health care use, and psychosocial adjustment in children with sickle cell disease (SCD); however, the mechanisms of the relationship are not clear. In this study, 41 children with SCD completed a laboratory pain task to analyze their pain perception under standardized conditions. Sensory decision theory analyses were used to analyze the pain perception data. Children and their parents also completed measures of coping strategies and adjustment. Hierarchical regression analyses controlling for the child's age indicated that children who reported using active cognitive and behavioral coping strategies had a lower tendency to report pain during the laboratory pain task. Results are discussed in terms of the utility of using laboratory pain models with children and the need for future intervention studies to target coping strategies in children with SCD pain.

Variation in the level of fetal hemoglobin (HbF) accounts for much of the clinical heterogeneity observed in patients with sickle cell disease (SCD). The HbF level has emerged as an important prognostic factor in both sickle cell pain and mortality, and a % HbF of 10-20% has been suggested as a threshold level for diminished clinical severity. The number of erythrocytes that contain HbF (termed F cells) may also be critically important, as F cells resist intravascular sickling and have preferential in vivo survival. Since F cells can be enumerated with high accuracy using flow cytometry methods, we prospectively studied a cohort of 242 children with SCD. Children with HbS and hereditary persistence of fetal hemoglobin (S/HPFH) had essentially 100% F cells. In contrast, children with homozygous sickle cell anemia (HbSS), HbS/beta0 thalassemia, or HbS/beta+ thalassemia had significantly lower mean % F cell values (55.9, 61.6, and 51.3%, respectively; P < 0.001), and children with HbSC had even fewer F cells (27.0%; P < 0.001). There was a highly significant correlation between the % F cells and the log (% HbF), which was observed for the total population of children (r = 0.95, P < 0.001), as well as for each of the individual subgroups of children with HbSS (r = 0.94, P < 0.001), HbSC (r = 0.89, P < 0.001), or HbS/beta0 thalassemia and HbS/beta+ thalassemia (r = 0.95, P

Adolescence is a time of intense change and turmoil. Helping patients with sickle cell disease have a smooth transition from the pediatric to adult health care environment is an important and meaningful experience. Facilitating the patient's transition, however, takes time and effort. Pediatricians must compile accurate medical summaries transmitting the details and nuances of the patient's history and care. Effort must be expended to ensure that details related to alloimmunization are not omitted. The pediatrician must be careful that the transfer does not create feelings of rejection and abandonment in the patient and the family. Physicians accepting the patient in transfer must devote time to educating and counseling the new patient. A relationship of trust and respect must be built. The physician should work with the patient to explore feelings of distrust and to uncover any concerns and fears, which should be dealt with proactively to avoid major conflicts later. Working closely with the adolescent patient can have many rewards, including helping the patient through a difficult period of adjustment. Helping the patient negotiate this difficult period can have many positive consequences. It is essential that both the pediatrician and internist work closely with the patient and family during the transfer process. Failure to do so can have disastrous consequences. When the collaboration is successful, however, the rewards for patients, families, and providers are great.

OBJECTIVES: (1) To determine serotype-specific IgG antibody responses to reimmunization with pneumococcal polysaccharide vaccine at age 5 years in children with sickle cell anemia and (2) to determine whether continued penicillin prophylaxis had any adverse effects on these responses. STUDY DESIGN: Children with sickle cell anemia, who had been treated with prophylactic penicillin for at least 2 years before their fifth birthday, were randomly selected at age 5 years to continue penicillin prophylaxis or to receive placebotreatment. These children had been immunized once or twice in early childhood with pneumococcal polysaccharide vaccine and were reimmunized at the time of randomization. RESULTS: Serotype-specific IgG antibody responses to reimmunization varied according to pneumococcal serotype but in general were mediocre or poor; the poorest response was to serotype 6B. The antibody responses were similar in subjects with continued penicillin prophylaxis or placebo treatment, and in subjects who received one or two pneumococcal vaccinations before reimmunization. The occurrence of pneumococcal bacteremia was associated with low IgG antibody concentrations to the infecting serotype. CONCLUSIONS: Reimmunization of children with sickle cell anemia who received pneumococcal polysaccharide vaccine at age 5 years induces limited production of serotype-specific IgG antibodies, regardless of previous pneumococcal vaccine history. Continued penicillin prophylaxis does not interfere with serotype-specific IgG antibody responses to reimmunization. (J Pediatr 1996;129:828-35)

From 1978 to 1988, The Cooperative Study of Sickle Cell Disease observed 3,765 patients with a mean follow-up of 5.3 +/- 2.0 years. One thousand seventy-nine surgical procedures were conducted on 717 patients (77% sickle cell anemia [SS], 14% sickle hemoglobin C disease [SC], 5.7% S beta zero thalassemia, 3% S beta zero + thalassemia). Sixty-nine percent had a single procedure, 21% had two procedures, and the remaining 11% had more than two procedures during the study follow- up. The most frequent procedure was abdominal surgery for cholecystectomy or splenectomy (24% of all surgical procedures, N = 258). Of these, 93% received blood transfusion, and there was no association between preoperative hemoglobin A level and complication rates (except reduction in pain crisis). Overall mortality within 30 days of a surgical procedure was 1.1% (12 deaths after 1,079 surgical procedures). Three deaths were considered to be related to the surgical procedure and/or anesthesia (0.3%). No deaths were reported in patients younger than 14 years of age. Sickle cell diseases (SCD)-related complications after surgery were more frequent in SS patients who received regional compared with general anesthesia (adjusted for risk level of the surgical procedure, patient age, and preoperative transfusion status, P = .058). Non-SCD-related postoperative complications were higher in both SS and SC patients who received regional compared with those who received general anesthesia (P =.095). Perioperative transfusion was associated with a lower rate of SCD- related postoperative complications for SS patients undergoing low-risk procedures (P = .006, adjusted for age and type of anesthesia), with crude rated of 12.9% without transfusion compared with 4.8% with transfusion. In SC patients, preoperative transfusion was beneficial for all surgical risk levels (P = .009). Thus, surgical procedures can be performed safely in patients with SCD.

Objective : To evaluate the consequences of discontinuing penicillin prophylaxis at 5 years of age in children with sickle cell anemia who had received prophylactic penicillin for much of their lives. Design : Randomized, double-blind, placebo-controlled trial. Setting : Eighteen teaching hospitals throughout the United States. Patients : Children with sickle cell anemia (hemoglobin SS or hemoglobin S β 0 -thalassemia) who had received prophylactic penicillin therapy for at least 2 years immediately before their fifth birthday and had received the 23-valent pneumococcal vaccine between 2 and 3 years of age and again at the time of randomization. Of 599 potential candidates, 400 were randomly selected and followed for an average of 3.2 years. Interventions : After randomization, patients received the study medication twice daily-either penicillin V potassium, 250 mg, or an identical placebo tablet. Patients were either seen in the clinic or contacted every 3 months thereafter for an interval history and dispensing of the study drug. A physical examination was scheduled every 6 months. Main outcome measures : The primary end point was a comparison of the incidence of bacteremia or meningitis caused by Streptococcus pneumoniae in children continuing penicillin prophylaxis versus those receiving the placebo. Results : Six children had a systemic infection caused by S. pneumoniae , four in the placebo group (2.0%; 95% confidence interval 0.5%, 5.0%) and two in the continued penicillin prophylaxis group (1.0%; 95% confidence interval 0.1%, 3.6%), with a relative risk of 0.5 (95% confidence interval 0.1, 2.7). All invasive isolates were either serotype 6(A or B) or serotype 23F. Four of the isolates were penicillin susceptible, and two (one from each treatment group) were penicillin and multiply antibiotic resistant. Adverse effects of the study drug were reported for three patients (nausea, vomiting, or both), one of whom was in the placebo group. Conclusion : Children with sickle cell anemia who have not had a prior severe pneumococcal infection or a splenectomy and are receiving comprehensive care may safely stop prophylactic penicillin therapy at 5 years of age. Parents must be aggressively counseled to seek medical attention for all febrile events in children with sickle cell anemia. (J PEDIATR 1995;127:685-90)

Although universal newborn screening can reliably identify all infants with sickle cell hemoglobinopathies, the initial screening result must not be considered the definitive diagnosis. We describe 23 infants whose screening phenotype was FS or FC but whose true phenotype included hemoglobin A, establishing a definitive diagnosis of hemoglobin S or hemoglobin C in combination with beta(+)-thalassemia. Higher than expected hemoglobin concentrations or lower than expected mean erythrocyte volumes should suggest concurrent beta(+)-thalassemia.

Children with sickle cell disease frequently present to the emergency department (ED) for evaluation of fever or management of pain. We retrospectively analyzed all ED visits by children with sickle hemoglobinopathies during 1990, excluding those for trauma. Of 146 visits by 56 children, 73 (50%) were classified as "Painful Events," 43 (29%) as "Febrile Events," 20 (14%) as "Painful and Febrile Events," and 10 (7%) as "Other." Hospital admission occurred for 42% of Painful Events versus 70% of Febrile Events (P = 0.008) and 85% of Painful and Febrile Events (P = 0.002). For Painful Events, location of pain was not associated with hospitalization, but pain less than 24 hours in duration before the ED visit (P = 0.002) and administration of intravenous fluids and analgesia (P = 0.001) were associated with admission. For children evaluated for Febrile Events, age less than six years (P = 0.016) and maximum temperature greater than 39 degrees C (P = 0.011) were associated with subsequent hospitalization, but total white blood cell count and absolute neutrophil count were not. For Painful and Febrile Events, pain less than 24 hours (P = 0.029) was associated with hospital admission, but age, maximum temperature, white blood cell count, and absolute neutrophil count were not. Although prospective studies are needed to validate these data, the identification of factors predictive of hospital admission should expedite ED care to sickle cell patients.

Rates of poor psychological adjustment of children with sickle cell disease remained relatively constant over initial and follow-up assessment points. However, there was relatively little stability in the classification of the adjustment of individuals, low congruence in specific behavior problem patterns and diagnoses in accordance with the Diagnostic and Statistical Manual of Mental Disorders (3rd ed.; American Psychiatric Association, 1980), and less stability in child adjustment by child report than by mother report. With initial levels of adjustment controlled, children's strategies for coping with pain accounted for a significant increment in child-reported symptoms (19%) and mother-reported internalizing behavior problems (8%) at follow-up beyond the contribution of illness and demographic parameters and follow-up interval. The findings suggest that children's coping strategies are a salient intervention target for enhancing adjustment.

Hemoglobin Lepore is composed of two normal alpha-globin chains and two delta-beta fusion globin chains that result from nonhomologous crossing over of genetic material during meiosis. The doubly heterozygous condition of sickle hemoglobin with Lepore hemoglobin (Hb S-Lepore) is rare, having been described previously in only nine patients. We report two siblings with Hb S-Lepore who have similar hematologic characteristics but a marked difference in clinical severity.

Assessed the psychological adjustment of 78 mothers of children and adolescents (7-17 years of age) with sickle cell disease. Support was provided for a transactional stress and coping model in delineating the processes associated with maternal adjustment. In particular, poor maternal adjustment was associated with use of palliative coping methods and high levels of stress related to daily hassles. Variables of the model accounted for 55% of the variance in maternal psychological distress.

Skin and nail changes from long-term hydroxyurea therapy are reported in adults. Skin and nail changes, including nail hyperpigmentation, longitudinal bands, and hyperpigmentation of the palms and other skin surfaces, developed in 7 children with sickle cell anemia after 6 to 16 weeks of hydroxyurea therapy. Cutaneous and nail changes may occur in children receiving hydroxyurea.

Twelve children underwent elective laparoscopic cholecystectomy for symptomatic cholelithiasis during a 10-month period in one institution. The operative technique that has been described for adults was modified because of the smaller dimensions of pediatric patients. These modifications are discussed in this report, as are new alternatives for evaluating the common duct. No operative complications or conversions to open cholecystectomy occurred, and no complications after surgery were seen during an average follow-up period of 4.5 months. The benefits of laparoscopic cholecystectomy include decreased pain and ileus after surgery, shortened hospitalization, and improved cosmesis. Laparoscopic cholecystectomy is safe and efficacious in children, and it compares favorably with traditional cholecystectomy in the pediatric age group.

Nine young patients with sickle hemoglobinopathies successfully underwent laparoscopic cholecystectomy; no complications resulted from the procedure. The mean postoperative hospital stay was 1.6 days. This technique appears to be a safe and efficacious procedure in children with sickle hemoglobinopathies who require cholecystectomy for cholelithiasis.

Acute episodes of pain are the principal symptom of sickle cell disease, but little is known about the epidemiologic features of these episodes or risk factors for them, nor is it known whether patients with high rates of such episodes die prematurely. We prospectively studied the natural history of sickle cell disease in 3578 patients ranging from newborns to persons up to 66 years old who were followed at clinical centers across the United States.There were 12,290 episodes of pain in 18,356 patient-years. The average rate was 0.8 episode per patient-year in sickle cell anemia, 1.0 episode per patient-year in sickle beta 0-thalassemia, and 0.4 episode per patient-year in hemoglobin SC disease and sickle beta(+)-thalassemia. The rate varied widely within each of these four groups--e.g., 39 percent of patients with sickle cell anemia had no episodes of pain, and 1 percent had more than six episodes per year. The 5.2 percent of patients with 3 to 10 episodes per year had 32.9 percent of all episodes. Among patients with sickle cell anemia who were more than 20 years old, those with high rates of pain episodes tended to die earlier than those with low rates. High rates were associated with a high hematocrit and low fetal hemoglobin levels. alpha-Thalassemia had no effect on pain apart from its association with an increased hematocrit.The "pain rate" (episodes per year) is a measure of clinical severity and correlates with early death in patients with sickle cell anemia over the age of 20. Even when the fetal hemoglobin level is low, one can predict that small increments in the level may have an ameliorating effect on the pain rate and may ultimately improve survival. This outcome is particularly encouraging to investigators studying hydroxyurea and other treatments designed to increase the fetal hemoglobin level.

In 1,814 patients with sickle cell disease who had been transfused, the overall rate of alloimmunization to erythrocyte antigens was 18.6%. The rate of alloimmunization in this group appears to be an explicit function of the number of transfusions received because it increases exponentially with increasing numbers of transfusions. Alloimmunization usually occurred with less than 15 transfusions, although the rate of alloimmunization continued to increase when more transfusions were given. The rate of alloimmunization was less in patients with hemoglobin SC disease and sickle-beta+ thalassemia because these patients had received fewer transfusions. Children less than 10 years old had a slightly lower rate of alloimmunization than patients in other age groups even after correction for the number of transfusions given. Women were more frequently alloimmunized than men; this was largely due to the fact that women received more transfusions than men, but in the age group 16 to 20 years the increase may have been due in part to alloimmunization owing to pregnancy. Forty-five percent of those alloimmunized made antibodies of only one specificity; 17% made four or more antibodies reacting with different antigens. Antibodies to the C and E antigens of the Rh group, the Kell antigen, and the Lewis antigens were most commonly made. These findings may be important in formulating a rational transfusion policy in sickle cell disease.

We describe our experience with 23 children with sickle cell disease and splenic sequestration crisis, emphasizing our management approaches and the patients' subsequent clinical courses. Our data illustrate that sequestration crisis may occur despite a reduction in hemoglobin S concentration to less than 30% of the total hemoglobin mass. In addition, the risk of recurrent splenic sequestration was similar for patients who received transfusion therapy and for those who were simply observed. We conclude that a short-term transfusion program to prevent recurrent splenic sequestration is of limited benefit.

We reviewed the clinical course, physical findings, and hematologic values in 16 pediatric patients with hemoglobin C disease, all but one identified by a newborn hemoglobinopathy screening program. The patients had a few symptoms or physical findings. Height and weight percentiles were normal. Patients typically had a mild hemolytic anemia characterized by microcytosis and target cells.

Ultrasonographic records of 75 children with sickle cell disease and hepatobiliary symptoms were reviewed. Seventeen had gallbladder sludge, nine with concurrent stones and eight with sludge alone. Because all the children eventually had gallstones, we recommend that elective cholecystectomy be performed on patients with gallbladder sludge.

The ability to identify infants with sickle cell anemia who are likely to have severe complications later in life would permit accurate prognostication and tailoring of therapy to match disease-related risks and facilitate planning of clinical trials. We attempted to define the features of such babies by following the clinical course of 392 children with sickle cell disease from infancy to about the age of 10 years.We analyzed the records of 392 infants who received the diagnosis of homozygous sickle cell anemia or sickle cell-Beta(0)-thalassemia before the age of six months and for whom comprehensive clinical and laboratory data were recorded prospectively; data were available for a mean (+/-SD) of 10.0+/-4.8 years. Results obtained before the age of two years were evaluated to determine whether they predicted the outcome later in life.Of the 392 infants in the cohort, 70 (18 percent) subsequently had an adverse outcome, defined as death (18 patients [26 percent]), stroke (25 [36 percent]) frequent pain (17 [24 percent]), or recurrent acute chest syndrome (10 [14 percent]). Using multivariate analysis, we found three statistically significant predictors of an adverse outcome: an episode of dactylitis before the age of one year (relative risk of an adverse outcome, 2.55; 95 percent confidence interval, 1.39 to 4.67), a hemoglobin level of less than 7 g per deciliter (relative risk, 2.47; 95 percent confidence interval, 1.14 to 5.33), and leukocytosis in the absence of infection (relative risk, 1.80; 95 percent confidence interval, 1.05 to 3.09).Three easily identifiable manifestations of sickle cell disease that may appear in the first two years of life (dactylitis, severe anemia, and leukocytosis) can help to predict the possibility of severe sickle cell disease later in life.

issues and purpose. Pain is the most frequent and important problem for children with sickle cell disease (SCD), but it has been undertreated and understudied. A multidisciplinary group of healthcare providers, academics, and people with SCD and their families met to (1) examine the pain of vaso-occlusive events (VOE) in children and adults with SCD and (2) reach consensus about necessary improvements in care. conclusions. Accurate assessment of pain is at the crux of effective care for children with VOE. This requires a trusting interactive relationship among patient, family, and healthcare team. Comprehensive pain assessment is a lifelong process in need of continued updating. practice implications. Children with SCD seek treatment from nurses in many settings. Traditional care has been frustrating to both families and care providers. Children and adolescents with SCD pain would benefit from nursing care that considers patients' perspectives about pain and comfort as key determinants for treatment. A unified approach to pain assessment may be a significant factor in improving pain control.

Purpose : This research was undertaken to determine the advantages, complications, costs, and efficacy of erythrocytapheresis in young pediatric patients who receive chronic erythrocyte transfusion therapy. Patients and Methods : We retrospectively analyzed data for 10 children who received erythrocytapheresis for an average of 16 months. Erythrocytapheresis was compared to simple transfusion therapy with respect to annual blood unit exposure, occurrence of alloimmunization, and costs. Serum ferritin levels were compared before and after the period of erythrocytapheresis. Results : Erythrocytapheresis was well tolerated, even in children as young as 5 years or as small as 20 kg. It required a greater annual unit exposure than simple transfusions, but did not increase alloimmunization. Ferritin levels decreased significantly in children receiving concurrent deferoxamine, and decreased or stabilized in those not on chelation therapy. Children started on erythrocytapheresis soon after stroke have not developed iron overload. Although the costs of erythrocytapheresis exceed that of simple transfusion, the substantial costs of deferoxamine therapy should be considered ; one child on erythrocytapheresis has been able to discontinue chelation therapy following normalization of his ferritin level. Conclusion : Erythrocytapheresis is a safe and effective method for young patients receiving chronic erythrocyte transfusions. Erythrocytapheresis can reduce total iron burden and may obviate the need for expensive chelation therapy.

Because high-dose oral dexamethasone therapy has been reported to be effective for adults with idiopathic thrombocytopenic purpura, we assessed the short-term efficacy and toxicity of dexamethasone in seven children with chronic or refractory idiopathic thrombocytopenic purpura. Dexamethasone therapy was effective and well tolerated; further long-term studies are warranted. (J P EDIATR 1996;128:281-3)

Found moderate stability in the classification of maternal adjustment in two longitudinal studies of mothers of children and adolescents with cystic fibrosis and sickle cell disease. In terms of the transactional stress and coping model, stable poor maternal adjustment was associated with higher levels of appraisal of daily stress and palliative coping and low levels of family supportiveness. With initial levels of maternal adjustment, demographic parameters, and follow-up interval controlled, concurrent levels of daily stress accounted for significant portions of variance in maternal adjustment at follow-up for both illness groups. In addition, illness severity, child psychological adjustment, and family conflict added significant increments to maternal adjustment at follow-up in the cystic fibrosis group. Findings are discussed in terms of a basis for subsequent intervention studies to enhance the adjustment of mothers of children with chronic illness.

Examined 9-month follow-up data obtained from children and adolescents with sickle cell disease (SCD) and their parents participating in a longitudinal study of pain coping strategies. Of 87 subjects completing the baseline assessment of pain coping strategies, 70 (80%) of their parents completed a structured pain interview assessing their child's health care use and activity reduction during painful episodes over the follow-up period. Regression analyses controlling for age and pain frequency revealed that baseline Coping Attempts were associated with higher levels of school, household, and social activity during painful episodes. Baseline Passive Adherence was associated with more frequent health care contacts during the subsequent 9 months. Increases in Negative Thinking over time were associated with further increases in health care contacts during the follow-up period. Comparing pain coping strategies assessed at baseline to pain coping strategies measured at follow-up revealed that pain coping strategies were relatively stable over time for younger children but changed more for adolescents.

Nine of 35 patients with sickle hemoglobinopathies and cholelithiasis were found to have concomitant common bile duct (CBD) stones. We describe the diagnosis and management of these patients with CBD stones. Historical information, physical examination, and routine laboratory tests were unable to identify accurately the patients with CBD stones. Similarly, ultrasonography of the hepatobiliary system was an insensitive method for detecting CBD stones, as only 3 of 8 patients were correctly identified. In contrast, both an intraoperative cholangiogram and endoscopic retrograde cholangiopancreatography were sensitive procedures for detection of CBD stones. We conclude that CBD stones are relatively common in patients with sickle cell disease and cholelithiasis, and clinicians should have a high index of suspicion for their presence.

Examined pain coping strategies in 72 children and adolescents with sickle cell disease and their parents using the Coping Strategies Questionnaire, and found that pain coping strategies could be reliably assessed. Children high on Negative Thinking and Passive Adherence were less active, required more health care services, and were more psychologically distressed during painful episodes. Children high on Coping Attempts were more active and required less frequent health care services. Parents high on Coping Attempts and low on Passive Adherence had children who were more active.

The distinction between transient erythroblastopenia of childhood (TEC) and congenital red cell aplasia (Blackfan-Diamond anemia) is usually possible at presentation using clinical and laboratory data. When hypoplastic anemia occurs in the first year of life, however, the distinction is more difficult. We describe 7 infants with hypoplastic anemia who illustrate this diagnostic dilemma.

Familial erythrophagocytic lymphohistiocytosis (FEL) is a rare disease of infancy and early childhood. Transmitted in an autosomal recessive manner, FEL is characterized by infiltration of lymphocytes and histiocytes into visceral organs, the bone marrow, and the central nervous system (CNS) [1,2,3]. Epipodophyllotoxin (VP-16) is currently the most effective chemotherapeutic agent against FEL; complete clinical remissions have been attained with this agent alone [4,5]. Prolonged remission has been achieved in only a few patients, usually those in whom aggressive systemic and CNS therapy was initiated early in the course of the disease [6]. For these children, the necessary duration of therapy has not been defined.

We report two patients who developed high urinary excretion of sodium chloride after receiving cisplatinum. One patient became symptomatically hyponatremic during intravenous administration of hypotonic fluid. The second patient developed orthostatic hypotension. Urine sodium and chloride concentrations exceeded 130 mmol/liter despite hyponatremia or volume depletion. There was no evidence of adrenal cortical impairment and no improvement with fludrocortisone. We propose that cisplatinum may inhibit solute transport by the thick ascending limb of Henle, causing clinically significant, previously unreported toxicity in patients receiving chronic cisplatinum antitumor therapy.

Lymphohistiocytic erythrophagocytosis (LE) is a usually fatal disease characterized by fever, organomegaly, hyperlipidemia, central nervous system involvement, and cellular immunodeficiency. Treatment with corticosteroids, cytotoxic chemotherapy, and blood exchange is unsuccessful. We have treated two children with the epipodophyllotoxin VP-16 and with intrathecal chemotherapy. Each patient had an initial complete response, and one remains in remission 36 months after therapy began. Aziridinylbenzoquinone (AZQ) therapy induced a complete response in a patient who relapsed during VP-16 therapy. A combination of VP-16 and intrathecal chemotherapy appears to be the most effective therapy for LE, and further evaluation of the role of AZQ is indicated.

The anaerobic diphtheroid Propionibacterium acnes was identified as the organism responsible for “shunt” nephritis in two adolescents with ventriculoatrial shunts inserted previously for the management of medulloblastoma. Only three cases of “shunt” nephritis secondary to infection with this common skin commensal organism are known to have been reported. The rarity of such reports may be related to the lack of good anaerobic laboratories, the length of time necessary for cultures to show growth, the poor ability of certain blood culture media to support growth of this organism, and the failure of physicians to consider Propionibacterium acnes as a true pathogen in certain clinical situations. Cancer 52:330-333, 1983.

The development of platelet alloimmunization is a common and potentially severe consequence in patients who receive frequent platelet transfusions. The use of single-donor pheresis units or human lymphocyte antigen (HLA)-matched platelets to prevent or delay the onset of alloimmunization is often unsuccessful. Once sensitization occurs and refractoriness to platelet transfusions develops, patients are at risk of severe bleeding which may be difficult to manage. There has been no reliably effective therapy for such patients once alloimmunization occurs. High-dose intravenous (IV) immunoglobulin therapy has been used to treat patients with autoimmune thrombocytopenia,1-4 autoimmune neutropenia,5,6 and posttransfusion purpura.7 Because of its success in these disorders, IV immunoglobulin was given to two patients with hemorrhagic symptoms who were refractory to platelet transfusions because of alloimmunization.

Current therapy for patients with trilateral retinoblastoma, consisting primarily of surgical intervention and radiotherapy, has resulted in no long-term survivors. The use of adjuvant chemotherapy has not improved this outcome. After observing a tumor response to cyclophosphamide in a patient with suprasellar retinoblastoma, we treated a subsequent patient with trilateral retinoblastoma with both vincristine and cyclophosphamide. Objective tumor regression resulted. Although the tumor ultimately progressed in both patients, these findings suggest that vincristine and cyclophosphamide are active in patients with intracranial (trilateral) retinoblastoma.

The role of Asp-beta 73 on the surface hydrophobicity and solubility of hemoglobin was studied using Hb A, Hb S, Hb C Harlem (alpha 2 beta 2Val-6,Asn-73), and Hb Korle Bu (alpha 2 beta 2Asn-73). The surface hydrophobicity of the oxy form of these hemoglobins increased in the order of Hb A, Hb Korle Bu, Hb S, and Hb C Harlem, coinciding with the change in solubility. The same is not true for deoxyhemoglobins. The solubilities of deoxy-Hb S and deoxy-Hb C Harlem were much lower than that expected from their surface hydrophobicity. Although the hydrophobicity of deoxy-Hb C Harlem is greater than that of deoxy-Hb S, the solubility of deoxy-Hb S is only one-third that of deoxy-Hb C Harlem. This deviation must be caused by the substitution of Asn for Asp at the beta 73 position and its inhibitory effect on hydrogen bonding in Hb S polymers. The kinetics of the polymerization of 1:1 mixtures of the deoxy form of S-C Harlem, A-C Harlem, Korle Bu-S, and Korle Bu-C Harlem were studied in comparison with that of deoxy-Hb S and deoxy-Hb C Harlem alone. All of these binary mixtures polymerized with a distinct delay time prior to polymerization. Based on the results of kinetic studies, the probability factors for nucleation of S-C Harlem, A-S, A-C Harlem, S-Korle Bu, and Korle Bu-C Harlem hybrid hemoglobins were calculated as 0.65, 0.5, 0.5, 0.15, and 0.17, respectively, in comparison with that of Hb S (1.0). The probability factor for Hb C Harlem alone was 0.3. These data suggest that the Asp-beta 73 is directly involved in nucleation during Hb S polymerization and that the beta 73 is always trans to the active Val-beta 6 in the formation of nuclei.