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Biomedical subjects

G R Serjeant

Publications and source records attributed to G R Serjeant.

At least 19 recordsLinked to original sources
PubMed2006

Bacteraemia in homozygous sickle cell disease in Africa: is pneumococcal prophylaxis justified?

BACKGROUND: The high frequency of Streptococcus pneumoniae as a cause of bacteraemia in homozygous sickle cell (SS) disease and its effective prevention has led to the routine use of pneumococcal prophylaxis in developed countries. The reported infrequency of this organism as a cause of bacteraemia in SS disease in Africa raises questions on the epidemiology of bacterial infection and on the need for pneumococcal prophylaxis in that continent. METHODS: A study of blood cultures in 155 Ugandan children (165 episodes) with SS disease and axillary temperatures of > or =38 degrees C, attending the University Teaching Hospital in Kampala (Uganda, East Africa). RESULTS: Positive blood cultures, obtained in 47/165 episodes, showed Staphylococcus aureus in 28 (60%) samples, Haemophilus influenzae in 9 (19%), Staphylococcus epidermidis in 4 (9%), and single cases of Streptococcus viridans, Escherichia coli and an unidentified Gram negative rod. Streptococcus pneumoniae was identified in only 3 (6%) episode. CONCLUSION: The infrequent isolation of Streptococcus pneumoniae from febrile children with SS disease in this study and in four other studies from Nigeria raises questions on a different spectrum of bacterial causes for bacteraemia in malarial areas. There are several possible explanations for this finding, but the data cast sufficient doubt on the case for pneumococcal prophylaxis for a controlled trial on its effectiveness in that environment to seem justified. These data are necessary to determine its role in African children and to provide the evidence base for healthcare authorities in equatorial Africa.

Adolescent↗
PubMed2005

Phenotype/genotype relationships in sickle cell disease: a pilot twin study.

The roles of genetic and non-genetic factors in the haematology, growth and clinical features of sickle cell disease have been studied in nine identical twin pairs (six homozygous sickle cell disease, three sickle cell-haemoglobin C disease). A comparison group of 350 age-gender matched sibling pairs, selected to have an age difference of <5 years, was used for assessing the concordance of numerical data. Attained height, weight at attained height, fetal haemoglobin, total haemoglobin, mean cell volume, mean cell haemoglobin and total bilirubin levels showed significantly greater correlation in identical twins than in siblings. Twins showed similarities in the prevalence and degree of splenomegaly, susceptibility to priapism, and in onset of menarche, but other clinical complications were discordant in prevalence and severity. These findings suggest that physical growth and many haematological characteristics are subject to genetic influences, but that non-genetic factors contribute to the variance in disease manifestations.

Adolescent↗
PubMed2005

Sickle haemoglobin and haemoglobin Stanleyville II: possible confusion with sickle cell-haemoglobin C disease.

OBJECTIVES: To bring to the attention of East African practitioners, the characteristics of Hb Stanleyville II, its interaction with HbS, and the resemblance of the double heterozygote to sickle cell-haemoglobin C (SC) disease. DATA SOURCES: A prospective study of 100 patients with Sickle Cell (SS) disease in the steady state attending the sickle cell Clinic at Mulago Hospital, Kampala, Uganda. STUDY SELECTION: Out of 100 patients with SS disease, two were also heterozygous for an alpha chain variant identified as Hb Stanleyville II. CONCLUSIONS: In association with HbS, Hb Stanleyville II produces a hybrid haemoglobin band which on alkaline haemoglobin electrophoresis, travels in the position of HbC. Such cases may cause confusion with sickle cell-haemoglobin C (SC) disease. The index cases in both families had associated alpha thalassaemia but from this small group, no conclusions may be drawn on the haematological or clinical significance of the interaction of Hb Stanleyville II with SS disease.

Adult↗
PubMed2003

Sickle cell disease in Uganda: a time for action.

OBJECTIVES: To draw attention to the extent of homozygous sickle cell (SS) disease as a public health problem in Uganda where a mean 20% frequency of the sickle cell trait implies that 25,000 babies with SS disease are born each year. To highlight the dangers of applying interventions developed in non-malarial areas to regions where malaria may change the natural history and outcome of sickle cell disease. DATA SOURCES: The published literature from Africa and from the US and Caribbean in populations of African ancestry. STUDY SELECTION: The world literature especially, that derived from the US, Caribbean, and equatorial Africa. DATA EXTRACTION AND SYNTHESIS: In non-malarial areas, simple interventions applied early in life have significantly improved survival and the quality of life. Two well documented interventions are pneumococcal prophylaxis and the early parental diagnosis of acute splenic sequestration. The available literature from Africa suggests that neither of these may be appropriate in malarial areas. CONCLUSIONS: Manifestations of SS disease differ in malarial areas and it is questionable whether interventions developed in non-malarial areas apply. There is an urgent need to document the causes of death so that locally appropriate interventions may be developed to improve survival. Equally urgent is the need to define the pattern of clinical problems so that models of care may be evolved for use in malarial areas. Without this knowledge, health care planners will not have the information necessary to develop strategies and limited resources may be inappropriately deployed.

Anemia, Sickle Cell↗
PubMed2001

Haematological response to parvovirus B19 infection in homozygous sickle-cell disease.

Infection with human parvovirus B19 is known to cause aplastic crises in patients with homozygous sickle-cell disease. We studied the haematological consequences of parvovirus B19 infection in 280 such patients who had been followed up from birth in Jamaica. Evidence of seroconversion was routinely sought with a baculovirus-based, enzyme immunoassay in serum samples taken during aplastic crises and in all stored annual serum samples. 70% of patients had seroconverted by age 20 years; of 177 infections, haematological change was typical of aplastic crises in 118 (67%), minor in 16 (9%), and not discernible in 43 (24%). This assay increased the detection of unsuspected seroconversion-an observation important in planning a strategy for parvovirus B19 immunisation.

Adolescent↗
PubMed2001

Mass spectral analysis of asymmetric hemoglobin hybrids: demonstration of Hb FS (alpha2gammabetaS) in sickle cell disease.

Formation of the asymmetric hemoglobin hybrid FS (alpha2gammabetaS) inhibits hemoglobin S (Hb S) polymerization in vitro and underlies the protective effect of fetal hemoglobin (Hb F) in homozygous sickle cell disease. Conventional methods for separating Hb reveal only symmetric Hb tetramers because of the rapid dissociation of tetramers to dimers relative to the separation time for electrophoresis and chromatography. To gain insight into the quantitative distribution of asymmetric Hb FS and other tetrameric species in sickle cell disease, the noncovalent association of Hb subunits in hemolysates was studied by a novel application of electrospray ionization mass spectrometry (ESI-MS). Mass spectra of both patient and fetal blood revealed predominance of tetrameric species with dimer and monomer subunits in lower abundance. ESI-MS analysis revealed the hybrid Hb AF (alpha2gammabetaA) in hemolysates shown by conventional high-performance liquid chromatography to contain only the symmetric species Hb A (alpha2betaA2) and Hb F (alpha2gamma2). A unique tetramer of average mass 64,558 Da was identified in hemolysates from patients with sickle cell disease in accordance with the calculated mass of the asymmetric Hb hybrid FS. Hybrid Hb species were stable under the ESI-MS conditions employed allowing concurrent determination of the proportions of Hb FS and the symmetrical Hb S (alpha2betaS2). The ratios of Hb FS to Hb S correlated closely (r2 = 0.96) with those predicted under physiological conditions.

Adolescent↗
PubMed2001

Foetal haemoglobin in homozygous sickle cell disease: a study of patients with low HBF levels.

High foetal haemoglobin (HbF) levels are believed to ameliorate the manifestations of homozygous sickle cell (SS) disease. The corollary implies that patients with low HbF levels should have more severe clinical courses. We investigated this in a retrospective study of 50 Jamaican patients with steady-state HbF levels below 1% compared with a control group (A) of 54 subjects with steady-state HbF levels between 2.5 and 3.4% (around the 25th centile for our population), and a second control group (B) of 60 patients with steady-state HbF levels between 4.6 and 5.2% (around the 50th centile). Comparisons across the groups indicated significantly fewer females in the study group (16, 50 and 57%, respectively). Examination for haematological trends across the groups showed positive linear trends for haemoglobin (Hb) (P=0.004), packed cell volume (PCV) (P=0.01), mean cell volume (MCV) (P= < 0.001), mean cell haemoglobin (MCH) (P= < 0.001) and a negative trend for haemoglobin A2 (P=0.03). Clinically, there were no differences in the incidence of painful crises, abdominal crises and the acute chest syndrome, but leg ulcers were significantly less frequent in the study group (P=0.04). Therefore low HbF levels do not appear to increase the clinical severity of SS disease and may be protective against leg ulceration.

Adolescent↗
PubMed2001

RBC transfusion in sickle cell anemia (HbSS): experience from the Jamaican Cohort Study.

BACKGROUND: RBC transfusion is widely advocated in the management of sickle cell anemia (SCA), but it carries potentially serious risks, especially in the setting of chronic transfusion. The Jamaican Sickle Cell Clinic is conservative in its use of transfusion, and this experience is presented to allow comparison with other centers in defining the role for transfusion in SCA. STUDY DESIGN AND METHODS: Reported here is a retrospective, descriptive study of all RBC transfusions given to 311 subjects with SCA who were followed in a cohort study from birth and are, at this writing, 16.3 to 24.7 years old. RESULTS: There were 520 transfusion episodes in 197 (63.3%) of the 311 subjects; 1 transfusion in 80 (41%) of those who received transfusion(s), 2 transfusions in 54 (27%), 3 transfusions in 21 (11%), 4 in 17 (9%), 5 in 9 (5%), and 6 or more in 16 (8%). Single transfusions were usual for acute anemia of aplastic crises or acute splenic sequestration, and multiple transfusions (up to 21 episodes) were usual in the prophylaxis of recurrent stroke. Indications were aplastic crisis (102), acute chest syndrome (90), acute splenic sequestration (75), stroke (62), septicemia (46), hypoplasia (40), hypersplenism (34), surgery (31), gastroenteritis (10), and miscellaneous (30). CONCLUSION: Despite conservative transfusion use, 70.6 percent of patients had received at least one transfusion by 20 years of age in the Jamaican Sickle Cell Clinic:

Adolescent↗
PubMed2001

Invasive pneumococcal disease in homozygous sickle cell disease: Jamaican experience 1973-1997.

OBJECTIVES: To examine the clinical features and epidemiology of invasive pneumococcal disease in homozygous sickle cell (SS) disease and the efficacy of pneumococcal prophylaxis. STUDY DESIGN: A retrospective study of 80 episodes in 68 patients in the Jamaican Sickle Cell Clinic in a 25-year period (1973-1997). RESULTS: Clinical features included a history of fever (94%), vomiting (70%), an ill appearance (80%), fever (89%), abnormal chest signs (43%), and meningismus (39%). There were 14 deaths-13 among 68 initial episodes (6 of which were deaths on arrival) and one death during a recurrence. Thirteen episodes occurred in patients who should have been receiving antibiotic prophylaxis. Ten were due to failure to adhere to protocols, and 3 occurred during prophylaxis; one patient was receiving oral erythromycin, and two had received injections of benzathine penicillin 4 and 24 days before the episode. All but one of the pneumococcal isolates were susceptible to penicillin. The 32 patients who received pneumococcal vaccine had more mild clinical courses as indicated by a greater chance of being treated as outpatients or surviving after admission (Mann-Whitney U test, P =.03). CONCLUSIONS: Penicillin remains the mainstay of prophylaxis, although breakthroughs occur and will become more common with the increasing frequency of penicillin-resistant organisms. Pneumococcal immunization appears to ameliorate the course of invasive disease.

Adolescent↗
PubMed2001

Cerebrovascular complications and parvovirus infection in homozygous sickle cell disease.

Human parvovirus B19 infection causes most clinically defined aplastic crises in homozygous sickle cell (SS) disease. With transfusion support, the outcome is generally benign; however, cerebrovascular complications in close temporal association with B19-induced aplastic crises have been described. We carried out a retrospective review, between 1978 and 1999, of 346 aplastic crises in patients with SS disease attending the Sickle Cell Clinic of the University Hospital of the West Indies, Kingston, Jamaica. Six cerebrovascular episodes, 5 with hemiplegia, occurred within 2 days of aplastic crises; and 4, all with features of encephalitis, occurred within 2 to 5 weeks. Hemiplegia in 2 children resolved completely, one is improving, and one persists 20 years later; one patient died from recurrent strokes. Of the 4 children whose events occurred later, all had seizure disorders and 2 had transient cortical blindness. The crude risk of cerebrovascular episodes in the 5-week interval after B19 infection was calculated as 58 times greater than expected, which is suggestive of a causal association.

Adolescent↗
PubMed2001

Significance of fever in Jamaican patients with homozygous sickle cell disease.

OBJECTIVE: To investigate the cause and outcome of high fever in Jamaican children with homozygous sickle cell disease. DESIGN: Retrospective review of febrile episodes in a three year period (1 September 1993 to 31 August 1996). SETTING: Sickle cell clinic, an outpatient clinic in Kingston run by the Medical Research Council Laboratories (Jamaica). PATIENTS: Patients with homozygous sickle cell disease under 17 years of age presenting with an axillary temperature >/= 39.0 degrees C (102.4 degrees F). MAIN OUTCOME MEASURES: Diagnosis, death. RESULTS: There were 165 events in 144 patients (66 (45.8%) boys) with a median age of 6.1 years. Bacteraemia was found in 10 (6.1%) events (three Streptococcus pneumoniae, two Haemophilus influenzae type b, two Salmonella sp, one Escherichia coli, one Enterobacter sp, and one Acinetobacter sp), and urinary tract infections in four (2.4%). All cultures of cerebrospinal fluid were sterile. Acute chest syndrome occurred in 36 (21.8%) events. A painful crisis was associated with 45 (27.3%) events and was the only pathology identified in 20 events (12.1%). Hospital admission was necessary in 66 cases including all those with bacteraemia and 31 with acute chest syndrome. There were two deaths: a 5 year old boy with septic shock associated with H influenzae septicaemia, and a 3 year old boy with the acute chest syndrome. CONCLUSIONS: Painful crisis and acute chest syndrome were the most common complications associated with high fever, but other important associated features included bacteraemia and urinary tract infection. Enteric Gram negative organisms accounted for 50% of positive blood cultures.

Adolescent↗
PubMed2001

Sickle cell disease and age at menarche in Jamaican girls: observations from a cohort study.

AIMS: (1) To investigate the distribution of age at menarche in a representative sample of 99 patients with homozygous sickle cell (SS) disease, 69 with sickle cell haemoglobin C (SC) disease, and 100 controls with a normal haemoglobin (AA) genotype followed in a cohort study from birth. (2) To explore the determinants of the age at menarche. METHODS: Children ascertained in a newborn screening programme were followed prospectively from birth to age 18-26.5 years with regular assessments of height, weight, pubertal stage, and haematological indices at the Sickle Cell Clinic of the University Hospital of the West Indies. RESULTS: All subjects have now reached menarche and the mean age in normal controls (13.0 years) was significantly earlier than in SC disease (13.5 years) or SS disease (15.4 years). Greater weight and earlier age at menarche was the only association significant across all genotypes although additional contributions occurred from fetal haemoglobin and red cell count in SS disease. Alpha thalassaemia, which ameliorates many of the effects of SS disease, had no discernible effect on menarche. CONCLUSIONS: Mean age at menarche is delayed by 0.5 years in SC disease and by 2.4 years in SS disease. Weight appears to be the principle determinant of age at menarche.

Adolescent↗
PubMed2000

Gallstones in sickle cell disease: observations from The Jamaican Cohort study.

The prevalence, incidence, risk factors, clinical associations, and morbidity of gallstones were studied in 311 patients with homozygous sickle cell disease and 167 patients with sickle cell-hemoglobin C disease in a cohort study from birth. Gallstones developed in 96 patients with homozygous sickle cell disease and 18 patients with sickle cell-hemoglobin C disease; specific symptoms necessitating cholecystectomy occurred in only 7 patients with homozygous sickle cell disease.

Adolescent↗
PubMed2000

Jamaican Sbeta+-thalassaemia: mutations and haematology.

The sickling disorders are a common cause of morbidity and mortality in Jamaica. Sickle cell beta+-thalassaemia is the fourth commonest form, occurring in one in every 3000 births. This is a heterogeneous condition, producing HbS, HbF and HbA2 with variable amounts of HbA, depending on the mutation and, within a defined population, only a few beta-thalassaemia mutations occur at high frequency. This study establishes the frequency of beta-thalassaemia mutations in Sbeta+-thalassaemia patients in Jamaica. In addition, comparison of the haematological phenotypes is possible by looking at the 'average steady-state haematology' of the different mutational groups. Blood samples from 132 unrelated Sbeta+-thalassaemia patients attending the MRC Sickle Cell Unit at the University of the West Indies were analysed by amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) or sequencing to determine the nature and frequencies of the underlying beta-thalassaemia mutations. Ten mutations were identified, four of which accounted for 93% of patients studied. These were -29(A --> G) in 71 (54%), -88(C --> T) in 27 (20%), polyA(T --> C) in 17 (13%) and IVS1-5(G --> C) in nine (7%). The six remaining mutations found at low frequency were C24(T --> A) in two patients and one each of IVS2-848(C --> A), -90(C --> T), IVS1-5(G --> T), IVS1-5(G --> A) and IVS1-6 (T --> C). In one individual, no mutation was found. The three commonest mutations were all associated with haemoglobin levels of greater than 10 g/dl, whereas IVS1-5 (G --> C) had a more severe haematological phenotype. The predominance of -29(A --> G) and -88(C --> T) is in keeping with other studies on populations of African origin. IVS1-5(G --> C) is found chiefly in Indian populations, and all affected families acknowledged Indian ancestry, reflecting the prominent Indian community in Jamaica.

Deoxyribonucleases, Type II Site-Specific↗
PubMed2000

Height and weight reference curves for homozygous sickle cell disease.

OBJECTIVE: To derive height and weight growth reference curves for children with homozygous sickle cell disease. STUDY DESIGN: Subjects (n = 315) were participants in a population based, longitudinal cohort study of sickle cell disease in Kingston, Jamaica. Regular measurements of height and weight were made from enrollment into the study at birth up to 22 years of age. RESULTS: Sex specific growth reference curves for height for age and weight for age covering the age range 0-18 years are presented. CONCLUSION: These growth reference curves are suitable for identifying coincidental growth problems in children with homozygous sickle cell disease.

Adolescent↗
PubMed2000

Psychological distress among younger siblings of patients with homozygous sickle cell disease in the Jamaican cohort study.

The presence of a chronically ill family member may adversely affect the psychological health of siblings. This study used the General Health Questionnaire and the Modified Social Adjustment Scale to assess psychological distress in 20 younger siblings (4 AA, 16 AS genotypes), aged 16-19 years, of patients with homozygous sickle cell (SS) disease. The results were compared with those previously obtained in the 20 older siblings with SS disease and in 89 controls with a normal haemoglobin (AA) genotype. High levels of psychological distress occurred among all three groups. Greater psychological distress and poorer social adjustment occurred among siblings compared to AA controls but these differences disappeared after adjusting for the reduced age of siblings. The two measures were similar in SS patients and AA controls. The level of psychological distress among siblings of SS patients did not differ from that in SS patients or AA controls.

Adolescent↗