Nephrotic syndrome in Nigerian children with homozygous sickle cell disease

Two hundred and seventy two children with the nephrotic syndrome were seen and followed up at the Paediatric Renal Unit of the University of Nigeria Teaching Hospital, Enugu over 12 1/2 year period, between June 1983 and December 1995. Of these, there were nine (3.3%) children with homozygous sickle cell disease (SS). This latter group had a mean age of 9.6 +/- 3.2 years, male to female ratio of 1:2 and serum cholesterol of 3.13 +/- 1.48 mmol/l at the time of diagnosis. The mortality rate was 55.6% in these sicklers, death occurring within one and a half to five years of diagnosis. Causes of death were attributable to sickle cell disease in 60%, renal diseases in 20%, and other causes in 20%. Renal biopsy in two of the sicklers showed membrano-proliferative glomerulonephritis (MPGN) and focal glomerulosclerosis (FGS) respectively. Homozygous sickle cell disease does seem to predispose to the development of the nephrotic syndrome and those that do develop nephrotic syndrome exhibit some special characteristics, when compared to non-sicklers with nephrotic syndrome. These include older age of onset of the nephrotic syndrome, reverse sex ratios, lower serum cholesterol, higher mortality rate and sickle cell complications rather than chronic renal failure as the major cause of death.     

Protein C activity in Gabonese children with sickle cell disease

Protein C levels were determined in 40 Gabonese children with sickle cell disease, in the steady state and during vasoocclusive crisis. In comparison with 40 healthy controls matched for age and sex, there was a significant decrease in protein C activity in the patients, although no difference was found between protein C levels in the steady state and during crisis.     

Acute splenic sequestration in hemoglobin sickle O-Arab disease

A white girl with sickle O-Arab disease (Hb S/O-Arab) had three separate episodes of acute splenic sequestration at 8, 12, and 15 months of age with hemoglobin levels falling to 3.9, 2.8, and 4.2 g/dl, respectively. Functional hyposplenism was suggested by the radionucleotide spleen scan. Following splenectomy her hemoglobin stabilized in the range of 0.7--8.5 g/dl. Life-threatening episodes of splenic sequestration, pneumococcal infections and osteomyelitis may occur in both Hb S/O-Arab and homozygous sickle cell diseases.     

Depiction of pain in the self-drawings of children with sickle cell disease

In an attempt to explore the perception of pain in children, 30 children with sickle cell disease were asked to make two drawings; one of themselves and one of themselves in pain. It was hypothesized that the cognitive ability and the emotional state of the child would be affected by the pain experience. Children and their parents were interviewed on the incidence of pain and on the child's control over it. The cognitive ability of the child was related to the kind of control he/she exercised over the pain. An analysis of the drawing concerning their thematic representations, colour and size is also presented. The mental age of the child dropped in the drawing of pain as compared to the non-pain drawing but it was found to be irrelevant to the kind of control the child exercised on the pain.     

Prothrombotic changes in children with sickle cell disease: relationships to cerebrovascular disease and transfusion

Vascular occlusion has a central role in the pathophysiology of sickle cell disease (SCD) and, although there is little evidence that thrombosis alone is responsible, patients with sickle cell disease are known to have an ill-defined but increased thrombotic risk. The most serious complication of this in childhood is stroke which occurs in 7-10% of children and a further 14% have asymptomatic cerebrovascular disease (CVD) on imaging. We have performed a comprehensive profile of coagulation inhibitors and markers of thrombin generation in 96 children (83 nontransfused [NTx] and 13 transfused [Tx]) with steady-state SCD and 18 healthy sibling controls. The levels of protein S (free and total) and heparin cofactor II were reduced in both the NTx and Tx groups compared to controls and protein C and APC resistance ratios were reduced in the NTx group only. Antithrombin levels were not different from controls. Thrombin-antithrombin complexes and prothrombin fragment F1+2 were increased in both patient groups. In the NTx subgroups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD. We conclude that children with SCD have a reduction in levels of the majority of the coagulation inhibitors and increased thrombin generation in the steady-state and these are only partially reversed by transfusion. However, these abnormalities do not appear to play a primary role in the development of cerebrovascular disease.     

Acute splenic sequestration together with aplastic crisis caused by human parvovirus B19 in patients with sickle cell disease

Three children with homozygous sickle cell disease, 22 months and 8 and 10 years of age, had clinical and hematologic manifestations of aplastic and splenic sequestration crisis simultaneously. They had an acute drop in hemoglobin level (16, 20, and 45 gm/L), reticulocytopenia (0.1%, 0.6%, and 0.3%), and sudden splenic enlargement. Evidence of recent parvovirus infection was demonstrated.     

Mortality of children with sickle cell disease in a pediatric department in Central Africa

BACKGROUND: Sickle cell disease is a serious public health problem in Gabon with a relatively high mortality rate. PATIENTS AND METHODS: Charts of 23 children (nine boys, 14 girls) who died of complications from sickle cell anemia in the department of pediatrics of Owendo Pediatric Hospital (Libreville, Gabon), from January 1, 1990 through December 31, 1992, were analysed retrospectively. RESULTS: Approximately two-thirds of the children (60.9%) were under 5 years of age. The great majority of patients were from low socio-economic standard families. Of 319 deaths observed during the study period, 23 were due to sickle cell disease-associated complications, for an overall mortality rate of 7.2% and a related mortality of 3.6%. Commonest causes of deaths were severe anemia (11 cases, i.e., 47.8%), which affected predominantly the younger patients between 6 months and 5 years (eight cases), infections (30.4%) and blood transfusion complications (21.7%). CONCLUSION: To decrease these mortality rates, appropriate health supervision and well-designed preventive strategies are needed.     

Platelet activation in patients with sickle cell disease

Vascular occlusion and vasculopathy underlie much of the morbidity in patients with sickle cell anaemia. Platelets may play a role in this vasculopathy. Samples from 43 patients with sickle cell disease (SCD) were examined for evidence of platelet activation using fluorescent-labelled monoclonal antibodies and flow cytometry. There was increased expression of activation-dependent antigens on the platelets from patients with SCD compared to those from both Caucasian and African-American controls. In addition, SCD patients had increased levels of platelet microparticles. Platelets are activated in patients with sickle cell disease. The contribution of platelet activation to sickle cell pathophysiology is under active investigation in our laboratories.     

National trends in the mortality of children with sickle cell disease, 1968 through 1992

OBJECTIVES: This paper describes national trends in mortality of children with sickle cell disease and the settings in which death occurred. METHODS: United States death certificate data from 1968 through 1992 were used to calculate mortality rates of Black children with sickle cell disease 1 to 14 years old. Deaths from trauma, congenital anomalies, and perinatal conditions were excluded. RESULTS: Between 1968 and 1992, mortality rates of Black children with sickle cell disease decreased 41% for 1- to 4-year-olds, 47% for 5- to 9-year-olds, and 53% for 10- to 14-year-olds. During 1986 through 1992, children who died before hospital admission accounted for 41% of deaths among 1- to 4-year-olds, 27% among 5- to 9-year-olds, and 12% among 10- to 14-year-olds. CONCLUSIONS: Survival of Black children with sickle cell disease has improved markedly since 1968. A substantial proportion of deaths continue to occur prior to hospital admission. Trends in sickle cell mortality can be monitored inexpensively with death-certificate data.     

Splenic sepsis in sickle cell disease

We describe two patients with sickle cell disease (SCD) who developed infections situated in the spleen. One patient had a splenic abscess and there was strong clinical evidence for an infected splenic infarct in the second patient. SCD predisposes to splenic infection because of functional hyposplenism, defective phagocyte function and splenic infarction. Splenic infections can occur in patients who might be considered to have an absent spleen and the diagnosis of splenic abscess should be considered in individuals with SCD who present with fever and abdominal pain.     

Management of the patient with sickle cell disease

A discrete neural circuit mediates the production of learned vocalizations in oscine songbirds. Although this circuit includes some bilateral pathways at midbrain and medullary levels, the forebrain components of the song control network are not directly connected across the midline. There have been no previous reports of bilateral projections from medullary and midbrain vocal control nuclei back to the forebrain song system, but the existence of such bilateral corollary discharge pathways was strongly suggested by the recent observation that unilateral stimulation of a forebrain song nucleus during singing leads to a rapid readjustment of premotor activity in the contralateral forebrain. In the present study, we used neuroanatomical tracers to demonstrate bilateral projections from (a) the rostral ventrolateral medulla (RVL), which may control respiratory aspects of vocalization, to nucleus uvaeformis (Uva), and (b) the dorsomedial intercollicular nucleus (DM), a midbrain vocal control region, to Uva. Both RVL and DM receive descending projections from the forebrain song nucleus robustus archistriatalis, and Uva projects directly to the forebrain song nuclei interfacialis and high vocal center. We suggest that the bilateral feedback projections from DM and RVL to Uva function to coordinate the two hemispheres during singing in adult songbirds and to convey internal feedback of premotor signals to the forebrain in young birds that are learning to sing.     

Multisystem damage associated with tricorporal priapism in sickle cell disease

It is demonstrated that fowlpox virus (FPV) protein FP26 located in the HindIII D fragment of the genome is related to the human deoxycytidine kinase (dCK) and probably possesses the same enzymatic activity. A homologous protein is not encoded by vaccinia virus. A multiple alignment of the amino acid sequences of the human and FPV dCKs, the thymidine kinases (TK) of herpesviruses, and cellular and vaccinia virus thymidylate kinases (ThyK) was generated and the conserved motifs, at least two of which are implicated in ATP binding, were characterized. An apparent duplication of ATP-binding motif B in the dCKs was revealed, leading to the reassignment of one of the catalytic residues. Phylogenetic analysis based on the multiple alignment suggested that the putative dCK of FPV probably has diverged from the common ancestor with the human dCK at a later stage of evolution than the herpesvirus TKs, with the ThyKs being peripheral members of the family. These results are compatible with hypothesis that genes for enzymes of nucleotide metabolism could be acquired independently by different DNA viruses (Koonin, E.V. and Senkevich, T.G., Virus Genes 6:187-196, 1992).     

Orbital compression syndrome in sickle cell disease

BACKGROUND: Orbital complications are an uncommonly reported finding in sickle cell disease. METHODS: The authors review the reported orbital manifestations of sickle cell disease and discuss a patient with hemoglobin sickle beta(0) thalassemia in whom rapidly progressive bilateral orbital compression developed. RESULTS: Computed tomography of the orbits in a patient with fever, headache, orbital swelling, and optic nerve dysfunction displayed bilateral superior subperiosteal cystic masses. Surgical exploration showed bilateral liquefied hematomas, which were evacuated. Recovery was complete 13 days after surgery. A mild recurrence 14 months later resolved with conservative treatment. The literature contains 11 reports of 16 young patients with sickle cell disease (15 sickle cell disease [Hb SS] and 1 hemoglobin sickle cell disease [Hb SC]) with rapidly developing findings ranging from frontal headache, fever, and eyelid edema to bilateral complete orbital compression syndrome. Including our patient, 60% had orbital hemorrhage on computed tomography. Ten of 12 patients tested were found to have orbital bone marrow infarctions. Sixteen of 17 patients had complete recovery; 13 were treated conservatively and 4 surgically. Only 2 of 17 had recurrence. CONCLUSIONS: Orbital complications in sickle cell disease are unusual manifestations in which a vaso-occlusive process in the marrow space around the orbit results in frontal headache, fever, eyelid edema, and often orbital compression syndrome. Subperiosteal hematomas are common and appear to result from bone marrow infarctions. Appropriate management requires a thorough evaluation to exclude other hemorrhagic, infectious or neoplastic processes, as well as vigilant ophthalmic monitoring. Supportive care is effective, unless optic nerve dysfunction or large hematomas are present, which would indicate that surgical evacuation is warranted to prevent loss of vision and to speed recovery.     

Quantitative MR imaging of children with sickle cell disease: striking T1 elevation in the thalamus

Nineteen patients with sickle cell disease (SCD) were examined with conventional MR imaging (cMRI), including T1- and T2-weighted sequences and MR angiography (MRA). qMRI mapping of T1 was also done using a precise and accurate inversion-recovery (PAIR) technique optimized and validated previously. In addition, 21 healthy African-American control subjects had the qMRI examination. Nonparametric Kruskal-Wallis analysis of variance of control subjects, of SCD patients without stroke, and of SCD patients with stroke showed that T1 increased with disease severity in the thalamus, frontal white matter, genu, and occipital white matter. T1 was significantly longer in SCD patients without stroke (n = 13) than in control subjects (n = 21) in the thalamus and frontal white matter. In addition, T1 values were significantly longer in SCD patients with stroke than in patients without stroke in the genu and frontal white matter. Abnormality of the thalamus was identified by qMRI in a substantial fraction of patients read as normal by both cMRI and MRA, suggesting that it may be possible to use T1 elevation to identify a subset of patients with SCD who are at elevated risk for stroke.     

Role of child and maternal processes in the psychological adjustment of children with sickle cell disease.

In this study, 64% of children aged 7–12 yrs with sickle cell disease were found to have a parent-reported behavior problem, and 50% met the criteria for a Diagnostic and Statistical Manual of Mental Disorders-III-Revised (DSM-III-R) diagnosis based on a structured clinical interview of the child. Internalizing types of behavior problems and diagnoses were the most frequent. Support was provided for a transactional stress and coping model in delineating the processes associated with child adjustment. In particular, maternal anxiety accounted for 16–33% of the variance in mother-reported internalizing and externalizing behavior problems, respectively, and child pain-coping strategies accounted for 21% of the variance in child-reported adjustment problems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Plasma and red cell lipids in sickle cell disease

Lipids, in particular phospholipids, are essential components of membrane systems, and the measurement of phospholipids and cholesterol in plasma and tissues is helpful in diagnosis. Phospholipids represent about 60 to 70% of total red cell (RBC) lipids, while about 25% is free cholesterol. Lipids in RBC are present in a dynamic state of equilibrium, and the RBC have the capacity for rapid exchange of lipids with plasma in several ways. The present study examined the cholesterol and phospholipid levels of plasma and erythrocytes in male patients with sickle cell anemia and in healthy male individuals of comparable age. This was performed with a view to detecting possible differences that might be related to some of the RBC abnormalities which accompany the disease. The results show that plasma lipids are significantly reduced in patients with sickle cell anemia and that RBC cholesterol was higher in sickle cell patients than in normal subjects.     

Psychosocial aspects of sickle cell disease

The study described in this article deals with sickle cell patients in Jamaica whose illness is accompanied by leg ulceration, a common complication of sickle cell disease. After exploring the disease's psychological, social, and economic effects, the authors suggest various ways for social workers to help sickle cell patients.