Multidimensional assessment of pain in pediatric sickle cell disease.

OBJECTIVE: To conduct a multidimensional assessment of pain in children with sickle cell disease (SCD). Variables included parent and child reports of pain location and intensity, qualitative descriptors of pain, perceptions regarding the seriousness and severity of SCD, and environmental and emotional factors associated with pain. METHODS: We replicated previous SCD pain research and applied advanced assessment methodology and research design to a population of pediatric SCD patients and their caregivers. RESULTS: Convergence of data supports the utility of multidimensional pain assessment with parents and children with SCD. SCD pain is experienced as intense and severe in home and hospital environments. CONCLUSIONS: Findings support including children as reporters in clinical assessment of SCD pain. Integration of assessment strategies into home-based pain management may improve health outcomes. Future research should target biobehavioral treatment for pediatric SCD pain.

Neuropsychological functioning of youths with sickle cell disease: comparison with non-chronically ill peers.

OBJECTIVE: To compare the neuropsychological functioning of children with sickle cell disease (SCD) with no evidence of overt clinical stroke to that of classmates without a chronic illness matched on gender, race, and age. We examined both overall level of performance and patterns of performance utilizing empirically derived construct scores of key domains of neurocognitive functioning. METHODS: An abbreviated neuropsychological battery of tests was given to 31 children with SCD and 31 case controls. Empirically derived construct scores were developed for primary analyses. RESULTS: Children with SCD had significantly lower scores on three level-of-performance construct scores: total, verbal, and attention/memory. Mean scores for children with SCD were lower than those for case controls on every level-of-performance construct score and every standardized test score. However, pattern-of-performance construct scores were not significantly different. CONCLUSIONS: Children with SCD without overt stroke demonstrate significant deficits in neurocognitive functioning compared to classroom case controls. These findings highlight the impact of SCD on general neurocognitive functioning and suggest that routine screening of cognitive functioning should be a requisite element of comprehensive care for children with SCD. Within the context of documented physical limitations, we conclude that children with SCD are at very high risk for impaired psychosocial outcomes.

Correlation of the C677T MTHFR genotype with homocysteine levels in children with sickle cell disease.

Recently, a mild to moderate elevation in the plasma homocysteine (Hcy) level has been found to be an important risk factor for stroke. Homozygosity for a common mutation (C677T) in the gene encoding for the enzyme methylenetetrahydrofolate reductase (MTHFR) involved in Hcy metabolism has been associated with increased levels of Hcy. To determine the role of hyperhomocysteinemia in the pathogenesis of stroke in children with sickle cell disease (SCD), Hcy levels and C677T MTHFR genotype were determined in 40 patients homozygous for hemoglobin SS and compared with 197 healthy children. Eleven of 40 patients with SCD had a history of stroke. The prevalence of homozygosity for the C677T MTHFR variant was 5% in the patients with SCD. The median Hcy level was 5.8 micromol/L in the patients versus 5.4 micromol/L in the controls (Fisher's, P > 0.05). There was no correlation of Hcy levels with the MTHFR genotype in patients with SCD. In patients with SCD and stroke, the median Hcy level was 4.8 micromol/L versus 6.0 micromol/L in those without stroke (P = 0.44, Mann-Whitney rank sum test). There was no difference in the proportion of patients with SCD with or without stroke who were homozygous for the C677T MTHFR mutation (0/11 versus 2/29; Fisher's, P = 1.000). In conclusion, this study failed to demonstrate an elevation in plasma Hcy levels in children with SCD compared with normal controls. Furthermore, hyperhomocysteinemia did not seem to be a significant factor in the pathogenesis of stroke in children with SCD.

Child-rearing practices of primary caregivers of children with sickle cell disease: the perspective of professionals and caregivers.

OBJECTIVE: To obtain caregiver and medical professional opinions regarding the child-rearing practices of caregivers of children with sickle cell diseases (SCD). METHODS: We obtained self-reports of parenting practices from 48 caregivers of children with SCD and 48 caregivers of matched classroom comparison peers using the Child-Rearing Practices Report (CRPR). CRPR ratings were also obtained from 12 experts in pediatric SCD regarding their predictions of how a parent of a child with SCD would respond. The experts predicted differences in protectiveness, discipline, and excessive worry. Objective interim and lifetime illness severity scores were obtained for the children with SCD. RESULTS: Caregivers showed similarity between the two groups, disagreement with the experts, and minimal relationship to illness severity. CONCLUSIONS: Experts who work with children with chronic illnesses such as SCD seem to have stereotyped ideas that do not correspond with parental reports of their child-rearing practices, suggesting the need for careful clinical evaluations.

Strokes, cutis marmorata telangiectatica congenita, and factor V Leiden.

Cutis marmorata telangiectatica congenita is an uncommon, congenital cutaneous condition typified by persistent cutis marmorata and other associated abnormalities. Progressive neurologic complications are generally not a feature of the disorder. A case is reported of cutis marmorata telangiectatica congenita associated with diffuse cerebrovascular infarcts at 7 months of age. Moyamoya-like vascular abnormalities were demonstrated in addition to the factor V Leiden mutation, a congenital hypercoagulable disorder. This novel case illustrates the importance of evaluating children with strokes for congenital thrombophilic disorders.

Serotype-specific immunoglobulin G antibody responses to pneumococcal polysaccharide vaccine in children with sickle cell anemia: effects of continued penicillin prophylaxis.

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 placebo treatment. 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.

Peer relationships and emotional well-being of youngsters with sickle cell disease.

Comparisons with measures of peer relationships and emotional well-being were made between youngsters with sickle cell disease (SCD) and same-classroom comparison peers. Relative to the comparison subjects, females with SCD were perceived by peers as being less sociable and less well accepted; males with SCD were perceived as being less aggressive than comparison peers. For both males and females with SCD, no other differences were identified on numerous measures of emotional well-being. None of the multiple measures of illness severity were significantly related to measures of psychological adjustment. The common side effects of SCD, chronic fatigue and small physical size, may divert males with the illness from manifesting difficulties related to aggressive behavior with peers. For females with the illness, the common side effects of the illness may hinder the development of normal social relationships. Despite chronic exposure to numerous stressful life events associated with SCD, the youngsters with the illness were remarkably similar to comparison peers, showing evidence of considerable hardiness.

Pre- and post-stroke MRI and neuropsychological studies in sickle cell disease: a case study.

The case of a patient with sickle cell disease is presented in which neuropsychological and magnetic resonance imaging studies were completed prior to and after a right hemispheric stroke. The contribution of a new MR perfusion technique in understanding the neurological complications in this patient is discussed. This case illustrates the complex pathophysiology of neuropsychological deficits in SCD and underscores the need to develop models that better reflect this complexity.

Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases.

BACKGROUND: This study was designed to determine the incidence of thoracic bone infarction in patients with sickle cell diseases who were hospitalized with acute chest or back pain above the diaphragm and to test the hypothesis that incentive spirometry can decrease the incidence of atelectasis and pulmonary infiltrates. METHODS: We conducted a prospective, randomized trial in 29 patients between 8 and 21 years of age with sickle cell diseases who had 38 episodes of acute chest or back pain above the diaphragm and were hospitalized. Each episode of pain was considered to be an independent event. At each hospitalization, patients with normal or unchanged chest radiographs on admission were randomly assigned to treatment with spirometry or to a control nonspirometry group. Each patient in the spirometry group took 10 maximal inspirations using an incentive spirometer every two hours between 8 a.m. and 10 p.m. and while awake during the night until the chest pain subsided. A second radiograph was obtained three or more days after admission, or sooner if clinically necessary, to determine the incidence of pulmonary complications. Bone scanning was performed no sooner than two days after hospital admission to determine the incidence of thoracic bone infarction. RESULTS: The incidence of thoracic bone infarction was 39.5 percent (15 of 38 hospitalizations). Pulmonary complications (atelectasis or infiltrates) developed during only 1 of 19 hospitalizations of patients assigned to the spirometry group, as compared with 8 of 19 hospitalizations of patients in the nonspirometry group (P = 0.019). Among patients with thoracic bone infarction, no pulmonary complications developed in those assigned to the spirometry group during a total of seven hospitalizations, whereas they developed during five of eight hospitalizations in the nonspirometry group (P = 0.025). CONCLUSIONS: Thoracic bone infarction is common in patients with sickle cell diseases who are hospitalized with acute chest pain. Incentive spirometry can prevent the pulmonary complications (atelectasis and infiltrates) associated with the acute chest syndrome in patients with sickle cell diseases who are hospitalized with chest or back pain above the diaphragm.

Bone marrow transplantation in a young child with sickle cell anemia.

Bone marrow transplantation (BMT) is the only curative therapy available for hemoglobinopathies. BMT was performed on a young child with sickle cell anemia (SCA) after approximately 9 months of transfusion therapy following her initial stroke. The patient received a matched sibling donor (sickle trait) BMT. The conditioning regimen consisted of busulfan 4 mg/kg/day x 4, cyclophosphamide 50 mg/kg/day x 4. Graft vs. host disease prophylaxis was daily cyclosporine for 6 months. There were no significant complications during BMT. Engraftment occurred on day +17 and the patient was transfusion independent since day +45. Pre-BMT cerebral arteriography showed multiple stenotic cerebral vessels and a moya-moya pattern. Perfusion MRI demonstrated reduced capillary perfusion. Approximately 170 days after BMT the patient experienced episodes of transient left-sided weakness and speech problems. Neuroimaging revealed progression of large vessel pathology by angiography despite significant improvement in cortical perfusion (MR perfusion scan). Molecular analysis by PCR and DNA fingerprinting confirmed absence of mixed mosaicism. Rheologic evaluation showed normal corrected bulk viscosity. It is possible that progression of large vessel pathology and return of clinical symptoms in the face of normal rheologic parameters may be due to worsening of the already damaged cerebral vessels by the BMT conditioning regimen. Further evaluations of patients with SCA undergoing BMT after a stroke are needed to answer this question.

Social competence of siblings of children with sickle cell anemia.

Examined the peer relationships of siblings of children with SCA (N = 37), comparing them to a matched group of classroom comparison children who were the same race/gender, closest date of birth. Social reputation was examined from the perspective of teacher and peers; peer ratings and nominations of social acceptance were obtained; and information was obtained about the sibling's own view of their peer relationships. No differences were found between the two groups, suggesting that the overall functioning of this group of siblings was comparable to peers in their classrooms. Findings are discussed in terms of professional biases, the lack of empirical data relevant to the issue of sibling competence, and resilience.

Sarcoidosis in a child with sickle cell anemia.

PURPOSE: The purpose of this case report is to (a) present a detailed description of a child with sickle cell anemia who developed sarcoidosis, (b) compare the clinical aspects of sickle cell anemia and sarcoidosis, and (c) review the literature with respect to the coincidence of these two diseases. Detailed clinical case history and laboratory findings are presented. A literature review of other case reports with children and adults who have both sickle cell anemia and sarcoidosis is given. RESULTS: Based on limited data, there may be an increased incidence of sarcoidosis in adults with sickle cell diseases. No data are available in the pediatric population. CONCLUSIONS: Sarcoidosis is difficult to diagnose in children with sickle cell anemia. The clinical manifestations of sickle cell anemia and sarcoidosis have overlapping features but represent distinct syndromes. Patients with sickle cell anemia who have unusual signs and symptoms need to be further evaluated for the possibility of other coincident diseases, including sarcoidosis.

Bone marrow transplantation for sickle cell disease. The United States experience.

PURPOSE: As of June 1992, five patients with sickle cell disease had been treated by matched sibling bone marrow transplantation in the United States. PATIENTS AND METHODS: Three patients underwent transplantations for complications related to sickle cell disease, two with previous cerebrovascular accidents (CVAs) and one who had had multiple severe vasoocclusive crises. Two patients had other indications for allogeneic bone marrow transplantation: one had acute myeloid leukemia and the other had Morquio's disease. The patients' ages ranged from 3 to 10 years, and four were girls. Ages of the donors ranged from 4 to 13 years; four of the donors were boys and three carried the sickle cell trait. For four patients, the preparative regimen consisted of busulfan and cyclophosphamide given either alone or combined with antithymocyte globulin (ATG). The patient with leukemia was prepared with cyclophosphamide and total body irradiation (TBI). The regimens for prophylaxis of graft-versus-host disease (GVHD) included various combinations of cyclosporine A, methotrexate, and prednisone. RESULTS: The patient with Morquio's disease failed to engraft but underwent a successful retransplantation from the same donor. All patients eventually demonstrated donor engraftment and the donor's hemoglobin electrophoretic pattern posttransplant. Two patients had moderately severe GVHD of the skin and gastrointestinal tract, which resolved with prednisone therapy. One of these patients developed transient chronic GVHD involving the skin. Other acute complications included mild venoocclusive disease of the liver, central line infection with bacteremias, uterine hemorrhage in one patient, and pseudomonas sepsis in another. CONCLUSIONS: Both patients who underwent transplantation after CVAs have experienced subsequent neurological events. However, with a median follow-up of 16 months (range 8 months to 9.3 years), all patients are surviving in good to excellent clinical condition and appear to have benefitted from treatment by bone marrow transplantation.

Simultaneous occurrence of rib infarction and pulmonary infiltrates in sickle cell disease patients with acute chest syndrome.

In order to determine if a relationship exists between rib infarction and the acute chest syndrome (ACS) in sickle cell disease patients, bone scans were reviewed in 55 episodes in 38 patients with pain of suspected osseous origin. A bone scan was positive for thoracic bone infarction if abnormally increased or decreased uptake was present in ribs, sternum or thoracic spine. Radiographs were considered to be positive for ACS if there was pulmonary infiltrate or pleural effusion in the absence of laboratory or clinical evidence of bacterial pneumonia. ACS by chest x-ray was present in 22 episodes, 21 of which showed evidence of infarction of the bony thorax on bone scan. Thoracic bone infarction occurred in the absence of chest x-ray changes in only 11 episodes. This association between bone infarction and radiographic ACS was statistically significant (p < 0.001, Fisher's exact test). A strong association exists between ACS and infarction of the bony thorax. It is possible that bone infarction leads to pain, hypoventilation and the clinical picture of ACS.

Rib infarcts and acute chest syndrome in sickle cell diseases.

In the absence of evidence for pneumonia or pulmonary embolus, primary pulmonary infarction has been assumed to be the cause of the syndrome of chest pain, fever, and pulmonary infiltrate on chest X-ray that commonly complicates sickle cell anaemia. To find out whether the syndrome might be due to rib infarction, 99mTc-diphosphonate bone scans were done. In the eleven episodes thus investigated (10 patients) the scans showed segmental areas of increased radionuclide uptake in ribs, indicative of bone infarction. A possible sequence of events is that the rib infarcts are primary and cause bone pain, followed by soft tissue reaction, pleuritis, and splinting. The resultant hypoventilation leads to atelectasis and subsequent development of the radiographic changes of the acute chest syndrome. Prevention of hypoventilation and treatment of bone pain are important therapeutic goals.

Value of screening umbilical cord blood for hemoglobinopathy.

Foremost among the beneficial effects of screening umbilical cord blood is the optimized quality of care that can follow the immediate involvement of an infant with sickle cell disease and his or her family in an appropriate health care system. This is exemplified by the reduction in the case fatality rate of pneumococcal septicemia that has been achieved. Appropriate follow-up of screening also includes transmission of information about the diagnosis of a hemoglobinopathy trait or alpha-thalassemia to affected families and their physicians, with ready availability of education and counseling.

Solid malignancies in children and adolescents.

The cure rate in childhood cancer has improved markedly during the past 20 years. In the 1960s the cure rate was about 20 to 30 per cent, but today more than 50 per cent of children and adolescents with cancer are being cured. This improvement is principally due to multidisciplinary teamwork in diagnosing, staging, and treating children with cancer; newer and more chemotherapeutic agents; and a recognition that combination therapy consisting of surgery, radiotherapy, and chemotherapy is frequently indicated.

Effects of dimaprit on growth and differentiation of human promyelocytic cell line, HL-60.

The human promyelocytic cell line HL-60, differentiates in response to a variety of agents including dibutyryl cAMP and agents which increase intracellular cAMP concentrations (phosphodiesterase inhibitors, PGE2, and cholera toxin). HL-60 is also known to be rich in H2 -histamine sensitive adenylate cyclase activity. The present study was therefore designed to test the effects of H2-stimulation on growth and differentiation of HL-60 using the potent H2 agonist dimaprit. Dimaprit markedly increased cAMP production in a dose-dependent manner reaching maximal levels after 30-60 minutes. Intracellular cAMP levels decreased thereafter and by 24 hours were approximately 2-3 fold increased above control. Intracellular cAMP levels were not altered by dimaprit (10(-7)M to 10(-4)M) at 4 days in culture compared to either untreated HL-60 cells or dimethylsulfoxide (DMSO) (1.3%) treated cells. While exponential growth was unaltered by dimaprit (10(-7)M to 10(-4)M) as compared to control, dimaprit induced i) morphologic maturation to the myelocyte and metamyelocyte form with no differentiation seen beyond the metamyelocyte even after 6 days in culture, ii) increased NBT reductase activity and iii) dose-dependent increase in lysozyme activity which could be completely blocked by cimetidine, a specific H2 antagonist. Dimaprit-induced differentiation of HL-60 cells was associated with an initial but transient increase in intracellular cAMP production. Maturation beyond the metamyelocyte stage was not observed. Acquisition of NBT reductase and lysozyme activity correlated with morphologic maturation.

Histamine H2 receptor desensitization in HL-60 human promyelocytic leukemia cells.

Recent studies have suggested that cyclic AMP (cAMP) may be involved in regulation of cell growth and differentiation of cancer cells. Incubating HL-60 cells in the presence of the specific H2 agonist dimaprit resulted in 30-fold increases in cAMP levels (EC50 = 5.7 X 10(-6) M) and morphological changes suggestive of cell maturation along the granulocyte pathway. However, cells cultured with 10(-5) M dimaprit showed more than an 80% decrease in their cAMP response to subsequent addition of H2 agonists, whereas the cAMP response to prostaglandin E2 was unaltered. Desensitization was time-dependent (halftime approximately 2.5 hr with 10(-5) M dimaprit), dose-dependent (dimaprit EC50 = 1.4 X 10(-6) M) and completely prevented by 10(-3) M cimetidine. Desensitization of HL-60 cells for 4 hr with 10(-5) M dimaprit followed by the addition of 10(-3) M cimetidine resulted in total recovery of the cAMP response in less than 24 hr. The pharmacologically inactive analog N-methyldimaprit (SK&F 92054) did not increase cAMP production or cause desensitization to H2 stimulation. Desensitization was observed in the presence or absence of a phosphodiesterase inhibitor, indicating that induction of cAMP-phosphodiesterase was not involved in this process. No difference in the number of [3H]tiotidine binding sites was observed between control and dimaprit-desensitized HL-60 cells. Based on these results, we suggest that H2 receptor agonists caused an agonist-dependent desensitization, presumably due to an uncoupling of receptors from adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)