Bacteriology of sickle cell leg ulcers.

The bacteria isolated on aerobic and anaerobic culture were compared in 80 unilateral ulcers in patients with homozygous sickle cell (SS) disease, 62 superficial skin lesions, and in 30 diabetic ulcers. In SS disease, the bacterial flora was predominantly aerobic and polymicrobial with Staphylococcus aureus, Pseudomonas aeruginosa and beta-haemolytic streptococci being the major isolates. Repeat sampling of 26 ulcers over a period of 23 weeks indicated the persistence of these three organisms, either singly or in combination in 21 ulcers.

Stilboestrol and stuttering priapism in homozygous sickle-cell disease.

A double-blind, placebo-controlled crossover study was conducted in 11 patients with stuttering attacks of priapism and homozygous sickle-cell (SS) disease. Stilboestrol 5 mg daily was better than the placebo in preventing attacks.

Pneumonia in young children with homozygous sickle cell disease: risk and clinical features.

The incidence and clinical features of pneumonia have been examined in children with homozygous sickle cell (SS) disease and in age/sex matched control children with a normal haemoglobin (AA) genotype followed in a cohort study of sickle cell disease from birth. Survival curve analysis indicated a similar incidence of pneumonia in the two genotypes up to the ages of 8 months after which pneumonia became significantly more prevalent in SS disease, the relative risk exceeding a factor of four by 4 years of age. Children with SS disease were also more prone to multiple episodes.

Recurrent visual loss in homozygous sickle cell disease.

In sickle cell retinopathy vascular involvement is most frequently recognised at the retinal periphery, but obstruction of perimacular arterioles and of major retinal vessels may also occur. This report describes a patient with homozygous sickle cell (SS) disease with recurrent occlusion of major retinal vessels associated with recurring transient impairment of visual function.

Acute splenic sequestration in homozygous sickle cell disease: natural history and management.

Of a cohort of 308 children with homozygous sickle cell disease diagnosed at birth, 89 experienced 132 clinically significant attacks of acute splenic sequestration (ASS) over a 10-year period. The age at first attack ranged from 3 months to 6 years. Survival curve analysis of the interval until first attack indicated a cumulative probability of 0.

Recurrent infections in sickle cell disease: haematological and immune studies.

Some haematological and immunological indices were compared in 19 children with sickle cell disease and a history of recurrent infections and in 16 children with sickle cell disease without any known infections. The recurrent infection group had significantly greater pitted red cell counts and greater absolute monocyte counts. No differences were apparent in routine haematological indices, foetal haemoglobin, immunoglobulin, or complement levels between the groups.

Haematological change in sickle cell-haemoglobin C disease and in sickle cell-beta thalassaemia: a cohort study from birth.

The haematological changes in early years following neonatal diagnosis have been observed in representative groups of children with sickle cell-haemoglobin C (SC) disease, sickle cell-beta(+) thalassaemia, and in sickle cell-beta(0) thalassaemia. Most haematological indices in SC disease were intermediate between previously published values in SS disease and in AA controls, generally being closer to values in normal children. Exceptions were microcytosis which may be genetically determined and a striking elevation of mean cell haemoglobin concentration from age 2 months to 4 years.

Clinical presentation of homozygous sickle cell disease.

The pattern of initial clinical symptoms and signs developing in a representative sample of 305 children with homozygous sickle cell (SS) disease diagnosed at birth was analyzed. Specific symptoms were present by age 6 months in 6% of the group, and had developed by the first to eighth birthdays in 32%, 61%, 78%, 86%, 90%, 92%, 94%, and 96%, respectively. Inclusion of nonspecific symptoms in the analysis led to earlier recognition by a mean of 3 months in the first year and by a mean of approximately 1 year between the ages of 2 and 4 years.

A genetic marker for elevated levels of haemoglobin F in homozygous sickle cell disease?

Ten patients with sickle cell (SS) disease from a Jamaican family were found to have unusually high levels of haemoglobin F for this population. Each of them has inherited one sickle cell gene on a chromosome characterized by an arrangement of restriction fragment length polymorphisms (haplotype) which is very rare in the Jamaican population. Genetic analysis of the family suggests that there is a determinant linked to the beta-globin gene cluster, characterized by this haplotype, which is responsible for increased haemoglobin F production in response to anaemia.

Alpha thalassemia changes erythrocyte heterogeneity in sickle cell disease.

Homozygous alpha-thalassemia has the beneficial effect in sickle cell anemia of reducing the hemolytic severity while changing several other hematological parameters. We examined in detail the cellular basis of some of these hematologic alterations. We find that the broad distribution in erythrocyte density and the large proportion of dense cells associated with sickle cell anemia are both reduced with coexisting alpha-thalassemia.

The haematology of steady state homozygous sickle cell disease: frequency distributions, variation with age and sex, longitudinal observations.

The steady state haematological characteristics observed in 1071 patients with homozygous sickle cell (SS) disease aged 5-66 years are presented. Cross sectional studies indicated that HbA2 levels were consistently higher in males but no age related change was apparent. Fetal haemoglobin levels were consistently higher in females and fell significantly in males between the 5-9 and 10-14 year age groups.

Treatment of sickle cell disease in early childhood in Jamaica.

The Jamaican sickle cell cohort study, based on neonatal diagnosis of all cases of sickle cell disease among 100,000 consecutive births, has identified acute splenic sequestration (ASS) and pneumococcal disease as the most important complications in early life. The etiology of ASS is unknown and prophylaxis is therefore not possible. For first attacks, attention has been directed to parental education to achieve earlier diagnosis.

Alpha thalassaemia and the haematology of normal Jamaican children.

Haematological indices were studied from birth to 9 years in a representative sample of 195 children with a normal haemoglobin (AA) genotype subdivided according to the number of alpha globin genes. These were 5 homozygotes for alpha-thalassaemia 2 (two-gene group), 60 heterozygotes for alpha-thalassaemia 2 (three-gene group), and 130 with a normal alpha globin gene complement (four-gene group). HbF and HbA2 showed no differences between the groups.

A randomized clinical trial of feeder vessel photocoagulation of proliferative sickle cell retinopathy. II. Update and analysis of risk factors.

Follow-up of patients enrolled in a randomized prospective trial of feeder vessel photocoagulation for proliferative sickle cell retinopathy has shown that photocoagulation is effective in preventing vitreous hemorrhage and visual loss from vitreous hemorrhage. In addition, a reduction of visual loss from all causes in photocoagulated eyes approaches statistical significance. Analysis of control eyes shows that there are three independent risk factors for the occurrence of vitreous hemorrhage: (1) the presence of the SC genotype, (2) the presence of vitreous blood at the initial evaluation and, (3) the presence of greater than 60 degrees of perfused neovascularization.

Production of F cells in sickle cell anemia: regulation by a genetic locus or loci separate from the beta-globin gene cluster.

Levels of fetal hemoglobin (HbF) bearing reticulocytes (F reticulocytes) range from 2% to 50% in patients with sickle cell (SS) anemia. To learn whether any portion of such variation in F cell production is regulated by loci genetically separable from the beta-globin gene cluster, percentages of F reticulocytes were compared in 59 sib pairs composed solely of SS members, including 40 pairs from Jamaica and 19 from the United States. We reasoned that differences in F reticulocyte levels might arise (1) from any of several kinds of artifact, (2) via half-sib status, or (3) because one or more genes regulating F cell production segregate separately from beta S.

Glomerular function and hyperuricaemia in sickle cell disease.

Renal insufficiency is common in adults with homozygous sickle cell disease, and the contribution of glomerular failure to the hyperuricaemia which is often a feature of the disease has therefore been investigated. In a study of 64 patients between the ages of 15 and 66, serum urate concentration was dependent on renal urate clearance and also on creatinine clearance. The relation between serum urate and creatinine clearance was abnormal in patients with sickle cell disease and it is suggested that this might be caused by high single nephron glomerular filtration rates.

Non-gouty arthritis in sickle cell disease: report of 37 consecutive cases.

Arthritis in association with sickle cell disease was seen in 37 patients in a 21/2-year period. Cases of gout and of avascular necrosis of the femoral head were excluded. In 12 patients a non-inflammatory effusion occurred during the course of a painful crisis, in 12 patients an ankle effusion occurred in association with spontaneous development or deterioration of leg ulceration, and in 13 patients there was a group of miscellaneous arthritides.

Interaction of the alpha alpha alpha globin gene haplotype and sickle haemoglobin.

We have studied the interaction of the alpha alpha alpha/alpha alpha gene arrangement with various beta globin genotypes (AA, AS, AC, SS and SC). Whereas this interaction has no detectable clinical or haematological effects in subjects with AA, SS or SC genotypes it is associated with a significantly increased level of Hb S or Hb C in heterozygotes for these variants. These findings indicate that the additional alpha globin gene in the alpha alpha alpha gene arrangement is functional.

G gamma beta+ hereditary persistence of fetal hemoglobin: cosmid cloning and identification of a specific mutation 5' to the G gamma gene.

Hereditary persistence of fetal hemoglobin (HPFH) is a benign condition in which the normal shutoff of fetal hemoglobin (Hb F) production fails to occur. In the G gamma beta+ type of HPFH, erythrocytes of adult heterozygotes contain approximately equal to 20% Hb F, which is almost exclusively of the G gamma-globin variety, without increased levels of gamma-globin chains from the nearby A gamma-globin gene. Unlike some forms of HPFH, no major deletions in the globin gene cluster have been found by genomic blotting in the G gamma beta+ variety.

Prevention of pneumococcal infection in children with homozygous sickle cell disease.

The efficacy of prophylactic penicillin and of 14 valent pneumococcal vaccine in preventing pneumococcal infection in homozygous sickle cell (SS) disease was investigated in 242 children aged 6 months to 3 years at entry. In the first five years of the trial there were 11 pneumococcal infections in the pneumococcal vaccine treated group, 10 by serotypes present in the vaccine. Type 23 accounted for five of these, and there was evidence of higher infection rates in those given the vaccine before age 1.

Blood rheology and proliferative retinopathy in sickle cell-haemoglobin C disease.

Haematological and rheological (plasma and serum viscosity, whole blood viscosity, and erythrocyte filterability) factors were studied in 31 age-sex matched pairs of patients with sickle cell haemoglobin C disease with and without proliferative sickle retinopathy (PSR). Patients with PSR had significantly higher mean cell haemoglobin and lower Hb F levels on average than the matched controls, but the viscosity and erythrocyte filtration indices did not differ between the 2 groups. There was, therefore, no evidence of rheological differences between patients with and without PSR at the time of the study, although transient rheological abnormalities at the time of development of PSR could not be excluded.

Mononuclear cells in sickle cell disease: subpopulations and in vitro response to mitogens.

The subpopulations of mononuclear cells and the lymphocyte proliferative capacity following mitogen stimulation were studied in 22 patients with homozygous sickle cell (SS) disease and 25 controls with a normal haemoglobin (AA) genotype. The total number of lymphocytes in peripheral blood samples was higher in SS patients compared to controls. Expressed as a percentage of total lymphocytes, the number of B lymphocytes (detected by membrane immunoglobulin fluorescence) was normal and of T lymphocytes (identified by sheep erythrocyte rosetting) was slightly reduced in SS disease.