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Biomedical subjects

R J Hayes

Publications and source records attributed to R J Hayes.

At least 127 records · Page 7Linked to original sources

Haematological factors associated with avascular necrosis of the femoral head in homozygous sickle cell disease.

The haematological indices in 50 patients with homozygous sickle cell (SS) disease and avascular necrosis of the femoral head and in 180 patients with SS disease without this complication have been compared. Avascular necrosis of the femoral head was significantly associated with high total haemoglobin levels and with low fetal haemoglobin levels. Low fetal haemoglobin levels are associated with increased intravascular sickling. These results suggest that both intravascular sickling and the increased viscosity associated with high haemoglobin levels are related to the development of avascular necrosis of the femoral head in SS disease.

Adult↗

Post-natal decline of fetal haemoglobin in homozygous sickle cell disease: relationship to parenteral Hb F levels.

The decline of fetal haemoglobin (Hb F) from birth to 6 years has been compared in a cohort of 266 Jamaican children with homozygous sickle cel (SS) disease and in 243 matched controls with a normal haemoglobin (AA) genotype. Hb F levels were significantly higher in the SS cases from 1 month onward but, unlike the normal controls, no sex difference was apparent. The Hb F levels in SS disease were significantly correlated with parental Hb F levels, suggesting that genetic factors regulating adult Hb F levels are active at earlier stages in development. Furthermore, some of these genetic determinants of Hb F production may be linked to the beta-like globin gene complex and be in linkage disequilibrium with the beta s allele.

Adolescent↗

Sickle cell retinopathy in young children in Jamaica.

Ophthalmological examinations were performed on 59 of the 74 (80%) children with homozygous sickle cell (SS) disease and on 37 of the 54 (69%) children with sickle cell-haemoglobin C (SC) disease, aged 5-7.5 years, within the cohort study of sickle cell disease. Arteriolar sheathing was the commonest retinal vessel abnormality, occurring in 30/59 (51%) SS children and in 11/37 (30%) SC children. Peripheral arteriolar closure was observed in 14 (24%) SS children and in 6 (16%) SC children. Arteriovenous anastomoses were seen in 3 children, but proliferative retinopathy was not identified. Capillary changes often occurred in patients without confluent closure, suggesting that complex remodelling of the capillary bed may precede retinal non-perfusion. Discrete retinal patches similar to schisis cavities resulting intraretinal haemorrhages were found in 22 (37%) SS children and in 9 (24%) SC children, but haemorrhages were observed in only 2 patients (1 SS, 1 SC). Vitreous opacities were common and were generally associated with retinal vessel disease. Retinal changes were consistently more common in children with SS disease, though the differences failed to reach statistical significance. The prevalence of peripheral vascular closure and retinal patches showed a significant upward trend with age. These observations contrast with the greater prevalence of proliferative retinopathy characterising SC disease in adults.

Anemia, Sickle Cell↗

Macular vasculature, visual acuity, and irreversibly sickled cells in homozygous sickle cell disease.

Observations of visual acuity and the conjunctival, macular, and perimacular vascularity have been assessed in patients with homozygous sickle cell (SS) disease. There were 17 matched pairs, each consisting of one patient with a high count (greater than or equal to 15%) and one with a low count (less than or equal to 5%) of irreversibly sickled cells (ISCs). The macular vascular bed was assessed by measurements of the foveal avascular zone (FAZ), perimacular avascular zones, and counts of perimacular vascular abnormalities (perimacular counts). Small foveal avascular zones and high perimacular counts were commoner in younger than older patients and there was a significant inverse correlation between size of the FAZ and the perimacular count. These observations were compatible with the hypothesis that perimacular vessel anomalies represent the early vaso-occlusive phase which progresses to ischaemia and the formation and enlargement of avascular areas. Visual acuity was assessed by Snellen's test type and by measuring contrast sensitivity. There was no obvious relationship between acuity measured by the 2 methods and no relationship between acuity and observations of macular vascularity. High ISC counts were significantly related to abnormalities of the conjunctival vasculature, but no relationship was noted with abnormalities of the macular vasculature or with visual acuity.

Adult↗

The interaction of N alpha-alkylenkephalins with opiate receptors. Tissue-dependent shifts in the opiate activity of methionine-enkephalin following N alpha-alkylation.

Experimental conditions for the small scale alkylation of the alpha-amino group of the opioid peptide methionine-enkephalin using the method of reductive alkylation are described. The generality of the method is established by describing in detail the synthesis, purification, and structure elucidation of the N alpha-ethyl, isopropyl, phenethyl, and cyclopropylmethyl derivatives of methionine-enkephalin. By a combination of amino acid and mass spectral analysis it is possible to carry out the structure analysis of nanomole quantities of these modified peptides, making direct chemical modification and structure elucidation of carrier-free tritiated and radioiodinated enkephalins feasible. Using these chemical procedures, a homologous series of N alpha-n-alkyl derivatives of methionine-enkephalin has has been synthesized. It is shown that the relative binding and opiate activity of these N alpha-alkyl derivatives, using several standard in vitro assay systems, depends on the tissue source used. The results of this study are analyzed by considering recent reports indicating the existence of multiple opiate receptors.

Alkylation↗

Fetal hemoglobin and clinical severity of homozygous sickle cell disease in early childhood.

The relationship of the clinical features of homozygous sickle cell disease in the first two years of life to the level of fetal hemoglobin at age 6 months was investigated. Mean HgbF levels were significantly lower in children manifesting early palpable splenomegaly, dactylitis, acute splenic sequestration, and in those who died. The risks of dactylitis and ASS were significantly greater in patients with lower HgbF levels. Since early splenomegaly itself may increase the risks of ASS, infection, and death, the relationship of HgbF to these features was further analyzed within the early splenomegaly group. The results suggest that a low HgbF may have a direct effect on the etiology of ASS, but any effect on infection or death is probably mediated via its relationship with the appearance of a palpable spleen. A protective effect of a high HgbF on the risk of dactylitis was demonstrated coincident with the accepted theory of its pathogenesis. Early HgbF determinations may be of value in identifying patients at high risk of serious complications during infancy.

Anemia, Sickle Cell↗

Haematological factors associated with proliferative retinopathy in homozygous sickle cell disease.

Haematological indices were investigated in 261 patients with homozygous sickle cell disease, 29 of whom had developed proliferative sickle retinopathy (PSR). After allowing for age-related effects, male patients with high Hb (> 9 g/dl) and low HbF (< 5%) levels appeared to constitute a high risk group for PSR. This relationship was not evident in females, PSR being observed in patients with lower Hb and higher HbF levels than in the male group. PSR occurred in 14% of patients aged 40 years or over in this sample.

Adolescent↗

Haematological factors associated with proliferative retinopathy in sickle cell-haemoglobin C disease.

In a selected sample of patients with sickle cell-haemoglobin C (SC) disease, proliferative retinopathy (PSR) occurred in 90/243 (37%) patients, developed most frequently between the ages of 20 and 30 years, and affected 68% patients aged 45 years or over. Comparison of haematological indices in patients with and without PSR, after age-related effects were allowed for, indicated significant relationships with high mean cell volume in males and with low fetal haemoglobin in both sexes. A highly significant relationship with total haemoglobin level in males (as previously reported in SS disease) was shown in SC disease to be entirely secondary to a strong age-related trend in haemoglobin level.

Adolescent↗

Priapism and impotence in homozygous sickle cell disease.

A questionnaire study of Jamaican patients with homozygous sickle cell (SS) disease indicated a 42% prevalence of priapism, with a median age at onset of 21 years. Two predominantly different patterns of priapism were recorded: short "stuttering" episodes lasting less than three hours, with normal consequent sexual function, and severe prolonged attacks (generally more than 24 hours) commonly followed by impotence. Stuttering episodes were frequently a prodrome to a major attack. Over one fourth of those who had suffered priapism had some degree of impotence. Hematologic analysis indicated that priapism was significantly associated with low hemoglobin F levels and high platelet counts. Patients with severe attacks of priapism had lower hemoglobin F levels and reticulocyte count, and a higher mean corpuscular volume, than patients with only stuttering episodes. Priapism and impotence contribute to the morbidity of SS disease more frequently than previously recognized.

Adolescent↗

Retinal and choroidal neovascularization in sickle cell disease.

Small vessel obstruction characterizes sickle cell disease and, when occurring in the peripheral retinal vessels, initiates a sequence of vascular events which may culminate in the development of proliferative sickle retinopathy (PSR). Repeated examinations of the retinal vasculature of patients with different genotypes of sickle cell disease over the last 10 years (Condon and Serjeant, 1972a, b, c; 1975; 1980a) have allowed observations on the natural history of PSR and on factors related to its development. Choroidal neovascularization has been a common complication of a trial of xenon arc photo-coagulation in PSR. Observations on the aetiology and natural history of both retinal and choroidal neovascularization are presented in this report.

Adolescent↗

Lack of an association between acute gastroenteritis, acute respiratory infections and malaria in young Gambian children.

The incidence of acute gastrointestinal and acute respiratory infections was measured in 2 groups of approximately 750 Gambian children aged 3-59 months during a 3-year period. One group of children was partially protected against malaria by fortnightly chemoprophylaxis with Maloprim whilst children in the other group were infected much more frequently. Mortality from acute gastroenteritis and from acute respiratory infections was similar in the 2 groups. The proportions of children in each group who complained of gastrointestinal or severe respiratory symptoms on morbidity surveillance were also similar. Thus, no evidence was found to suggest that malaria plays either a direct or indirect role in causing acute gastrointestinal or respiratory infections in young children in The Gambia.

Acute Disease↗

Antibodies to blood stage antigens of Plasmodium falciparum in rural Gambians and their relation to protection against infection.

Cross-sectional and longitudinal studies were performed in a rural population living in The Gambia to examine the relationship between several in vitro assays of the host immune response to asexual stages of Plasmodium falciparum and protection from malaria in vivo. Assays included an enzyme-linked immunosorbent assay for antibodies to schizont antigens; an indirect immunofluorescence assay for total antiblood-stage antibodies; an immunofluorescence assay on glutaraldehyde-fixed parasites to detect antibodies to antigen Pf 155; an assay for serum inhibition of red blood cell invasion; a micro-agglutination assay to detect antibodies to neo-antigens on the surface of infected red blood cells; and an assay using polymorphonuclear leucocytes to detect antibodies capable of opsonizing schizont infected red blood cells. There were marked differences in the age-related pattern of response for different assays performed on sera obtained at a cross-sectional survey of 280 individuals. Examination of the correlation between the various immune responses and malariometric indices at the population level and at the individual level provided no evidence that any of the in vitro assays were related to protective immunity. The relationship between in vitro measurements of the anti-malarial immune response and protection from clinical episodes of malaria was examined in a group of 134 children aged 11 years and under who were monitored weekly throughout an entire malaria transmission season. The only immune factor to show a consistent protective effect against clinical malaria was the titre of antibodies to neo-antigens on the infected erythrocyte surface (P = 0.01). The same longitudinal techniques were used to examine the effect of two non-immunological factors, sickle cell trait and mosquito net usage, both of which showed significant protection against clinical episodes and malaria.

Age Factors↗

Nutritional status and risk of morbidity among young Gambian children allowing for social and environmental factors.

A prospective study of the relationship between anthropometric indices and subsequent morbidity was conducted during 2 seasons in young children in an urban Gambian community. Children with low height-for-age at the beginning of the rainy season had a significantly higher prevalence of diarrhoea and fever during the next 4 months, even after controlling for the possible confounding effects of a range of social, economic and environmental factors. The association was weaker in the dry season. This indicates that the increased prevalence of symptoms among stunted children is not solely attributable to environmental factors, and suggests that impaired growth is associated with impaired host response to infection.

Child, Preschool↗

Sustained protection against mortality and morbidity from malaria in rural Gambian children by chemoprophylaxis given by village health workers.

Mortality and morbidity from malaria were measured in children for a one-year period in a rural area of The Gambia 3-4 years after the introduction of a primary health care programme into some villages in the study area. Among children resident in primary health care villages who received treatment for febrile illnesses from a village health worker resident in their village there was no reduction in overall mortality or in morbidity from malaria compared with levels found in villages without a primary health care worker. However, among children aged 3-59 months who received malaria chemoprophylaxis from a village health worker in addition to treatment there was a 49% reduction in mortality and a 73% reduction in attacks of clinical malaria. The level of protection against malaria achieved by chemoprophylaxis given by village health workers 3-4 years after the chemoprophylaxis programme was started was as high as that obtained shortly after the introduction of the primary health care programme.

Antimalarials↗