Haemoglobin D in Jamaica

In 11 of 550 persons of African descent living in a rural district in Jamaica, a haemoglobin with the properties of Haemoglobin D trait was uncovered in family studies and a close degree of relationship between them was demonstrated with the possibility of a common ancestor. Haemoglobin D consists of 3 different haemoglobins, appears identical with that found in India and is not associated with the African races (the only instances in Africa having been reported from the Congo). Speculation as to its origin must await further study (AU)

High incidence of haemoglobin G[Accra] in a rural district in Jamaica

The findings of Hb G Accra in 2.3 percent of a rural population in Jamaica is reported. This haemoglobin, originally found in one Negro family in West Africa, has never been reported again from Africa or anywhere else in the world. The significance of the high incidence of this abnormal haemoglobin in a random sample of the population is discussed and attributed to inbreeding in a relatively static community. (Summary)

Modern laboratory methods in clinical haematology: the assay of serum vitamin B12

A simple microbiological method for assaying vitamin B12 in serum is described and the levels in normal subjects, hospital patients without anaemia, ante-natal mothers, infants and patients with pernicious anaemia in Jamaica are recorded and compared (AU)

Oxygen transport in sickle cell anemia

Oxygen transport and delivery in sickle cell anemia are discussed in terms of hemodynamics and blood oxygen affinity. The current concepts of the regulation of the hematocrit value by the oxygen pressure on the venous side of the renal capillary are reviewed, and the concept of 'anemia' redifined. The marked right shift in the oxygen dissociation curve of sickle cell anemia blood is analyzed in terms of the sickling process, the hemolytic anemia, and increase in 2.3 diphosphoglycerate. The clinical implications of this right shift in perpetuating sickling are discussed in the light of its possible correction by treatment with sodium cyanate (AU)

Glucose-6-phosphate dehydrogenase deficiency and methaemoglobin reduction in sickle cell anaemia - abstract only

Red cell glucose-6-phosphate dehydrogenase (G6PD) deficiency is inherited as an X-linked condition with full expression in males and homozygous females, who can be detected by assay of their red cell enzyme activity and by various simple tests. G6PD converts glucose-6-phosphate (GSP) to 6-phosphogluconate (6PG), thereby making hydrogen available for the reduction of the nucleotide nicotine-adenine dinucleotide phosphate (here referred to as TPN) to its reduced form (TPNH), which may be measured by its absorbance at 340 millimicrons. The TPNH formed as a result of G6PD activity is available for the reduction of oxidised glutathione (GSSG) and methaemoglobin and thus protects the red cell from the effects of oxidants and oxidant drugs. In erythrocytes with normal G6PD levels the pathway is strongly stimulated by the presence of small quantities of methylene blue. Brewer's test, which takes advantage of this stimulation, has been widely used to detect G6PD deficiency. It was reported recently from West Africa that there is an association between sickling and G6PD deficiency; Brewer's test indicates that, in that area, some 28 percentof sickle cell traits (Hb AS) and 48 percentof sickle cell anaemias (Hb SS) are deficient, whilst only 14 percentof controls (Hb AA) are deficient. Such an association requires the existence of strong forces of natural selection in favour of the double genetic defect and the workers in West Africa suggest that G6PD-deficient sickle cell anaemia patients have such an advantage. In Jamaica, 13 percentof males are G6PD-deficient and, as sickle cell anaemia is common, it was decided to investigate the incidence of the deficiency in sickle cell patients. Three methods for detecting G6PD deficiency were employed, viz.(1) Sass' method, involving the reduction of methylene blue, (2) the G6PD assay by TPN reduction, (3) the nitrite-free reduction of methaemoglobin in the presence of methylene blue (modified Brewer's test). The deficiency in males and homozygous females was detected by the first two methods. As expected, faster methaemoglobin reduction rates and higher G6PD assay levels were found for sickle cell anaemia blood than for normal blood. With the modified Brewer's test, the initial methaemoglobin reduction rate was found to be independent of the haemoglobin type, but dependent on the G6PD assay levels. The reaction showed approximately zero-order kinetics when sufficient G6PD was present but tended to first-order behaviour when G6PD was low. Blood from some females had methaemoglobin reduction behaviour with a tendency towards first-order kinetics but a rate and G6PD level within the normal range. These are probably heterozygous, with uneven distribution of the enzyme in their red cell. They can be detected with the Sass m ethylene blue test if the dividing line between normal and deficient blood is lowered to allow for the effect of increased G6PD in sickle cell anaemia generally. By these tests, 7 1/2 per cent of males and 12 per cent of females with sickle cell anemia are relatively G6PD deficient, which is a lower incidence than expected and does not support the hypothesis that there is a natural selection of these two mutant genes. (AU)

Urinary figlu and serum B12 levels in patients with anemia

In a study of 32 anaemic patients (Hb less than 7.5gm percent) it was found that all patients with normoblastic marrow had negative urinary figlus. No case of ankylostomiasis demonstrated deficiency of folic acid or B12. The survey is to continue wuth emphasis on th megaloblastic anaemias (AU)

Hereditary hypochromic anaemia with iron loading

An unusual case was reported in which a 24 year old Jamaican male was found to have a constitutional defect of iron metabolism involving the utilization of pyridoxine in hemoglobin formation. It was found that pharmacological doses of Vit B6 allowed a greater rate of haemoglobin formation without altering the fundamental defect which caused iron accummulation in the body (AU)

Alpha thalassaemia phenotypes

The effects of deficient alpha chain synthesis at the clinical and subclinical level are illustrated by observations on 17 members of a family of mixed Chinese-Scottish-Negro origins. The presence of beta thalassaemia and its variants and the haemoglobin structural mutants have been excluded by presently available methods. The family includes 5 cases of Hb H disease, 3 cases of classical alpha thalassaemia trait and two adult subjects presumed to carry "silent" alpha thalassaemia gene. Clinical and laboratory aspects are presented (AU)

Irreversibly sickled erythrocytes: a consequence of the heterogeneous distribution of hemoglobin types in sickle-cell anemia

The amount of fetal hemoglobin (Hb F) in erythrocytes of patients with sickle cell anemia (Hb SS disease) was measured by two methods: (a) photometry of individual cells strained for Hb F by the Kleihauer-Betke technique; and (b) chemical assay of alkali-resistant hemoglobin in cells distributed according to specific gravity by ultracentrifugation. Irreversibly sickled cells (ISC), which could be identified directly during photometry and which were found to gather in high concentration at the bottom of ultracentrifuged cell columns, contained significantly less Hb F than non-ISC. Cell content of total Hb was constant regardless of cell size, shape, or ultracentrifugal behavior: thus absolute amounts of Hb F and S varied reciprocally from cell to cell. In experiments designed to estimate age, at formation, and rate of destruction of ISC, Hb SS blood was incubated with selenomethionine-75Se (which labels reticulocytes) of 51Cr (which labels erythrocytes at random) and reinfused. Sequential blood samples were separated by ultracentrifugation into fractions rich in reticulocytes, non-ISC, ans ISC; and chronological changes in the specific activity of each fraction were determined. Analogous information was obtained from radioautography of sequential blood samples after reinfusion of whole blood labeled with amino acids-3H: this technique permitted direct visual characterization of labeled erythrocytes as ISC of non-ISC, all of which had been reticulocytes at the time of reinfusion. The transformation of non-ISC into ISC, presumably a manifestation of membrane damage, proved to begin soon after cell release from the marrow; and ISC subsequently underwent rapid removal from the circulating blood. It is therefore apparent from these studies that, in Hb SS disease, relatively small reciprocal changes in the amounts of the two major hemoglobins carry predictive importance: (a) net synthesis of Hb F is least in erythroid cells destined to become ISC; and (b) these irreversibly deformed erythrocytes suffer preferential destruction. (AU)

The management of leg ulcers in sickle cell anaemia

The incidence of skin ulceration of the lower leg in patients suffering from sickle cell anaemia was found to be 46.1 per cent in patients attending the Sickle Cell Anaemia Clinic at the University College Hospital of the West Indies in Jamaica. The results of pinch grafting in thirteen cases are reported in detail. The importance of after-care to prevent breakdown of the grafted site is stressed and, because of the simplicity of the method and encouraging results, a plea is made for the wider use of this technique in the care of patients with sickle cell anaemia (AU)

Haemoglobin-H disease due to a unique haemoglobin variant with an elongated O-chain

The clinical and genetic properties of an unusual O-chain variant of human haemoglobin are described. It constitutes less than 1 percent of the total haemoglobin in heterozygotes and, when inherited together with an O-thalassaemia gene, produces the clinical picture of haemoglobin-H disease. Preliminary structural studies indicatge that, in addition to the 141 aminoacid residues which constitute the normal O-chain, this variant has about 31 extra residues attached to the C-terminal end.(SUMMARY)

Haemoglobin H disease caused by alpha-thalassaemia and a new abnormal haemoglobin with an elongated alpha-chain (Hb constant spring) - abstract

Of the 120 or so variants of human haemoglobin polypeptide chains so far described, nearly all are the result of the substitution of a single amino acid residue for another, or a deletion of one or more residues in the chain, caused by a point mutation in the codens of the chromosomal DNA. Hb H disease is also a genetically determined haemolytic anaemia, common in Orientals, but is caused by a reduced rate of synthesis of the O-chain of normal haemoglobin, resulting in an excess of á-chains (Hb H). A study of a Chinese family in Jamaica has revealed a slow moving haemoglobin in three children who have clinical haemoglobin H disease and in their fathers and siblings who have no haematological abnormality. The mothers have classical O-thalassaemia trait, as do some of the other siblings. Detailed biochemical analysis of this variant has shown that the O-chain is abnormal and is elongated by the addition of 31 residues to the 141 of the normal OA-chain. The extra residues are continuous with the normal C-terminal (O-141 Arg.) Biosynthetic studies, incorporating H(to 3rd power) leucine have indicated a low rate of synthesis for this abnormal chain. Interest lies in the nature of the genetic defect which could produce this abnormalty. While considering several hypotheses, the authors favour the theory that the genetic codon for 'end of chain' is the site of a mutation. This hypothesis is strengthened by finding Glutamine to be the next residue after the C-terminal Arginine. This extra piece of chain bears no resemblance to any known human globin chain sequence, so that it is unlikely that it has resulted from an unequal crossing over in a similar way to the Lepore haemoglobins. It may be that the messenge RNA for the normal OA-chain is longer than is required to direct synthesis of the chain. Further studies are in progress to try and define the nature of this genetic defect (AU)

Absorption of dietary iron and ferrous ascorbate by infants - abstract

There is no substantial evidence in adults that only a small proportion of the iron, chemically measured, in various foodstuffs is available for absorption. Hussain et al showed that only about 4.5 per cent of the iron present in wheat is absorbed by a normal adult whereas 12 per cent of the iron in ingested blood is absorbed. Even in the presence of iron deficiency the absorption of iron from carbohydrate foods is only marginally improved. In adults the iron absorbed from cooked soybean meal has been found to be better than that from any other vegetable source, and as the iron content of this food stuff is relatively high, it could be a useful source of iron for the infant. Absorption tests were carried out in 'normal' infants and treated malnourished infants, 9 months to 15 months old, using a whole body radioactivity counter and feeding corn or soybean meal which had radioactive iron (Fe59) incorporated into the plants during cultivation. The meals were arranged to contain 0.5 mg of iron and radioactivity remaining in the body at 7 days was used to calculate the percentage of iron absorbed. Test were repeated in the fasting subjects using ferrous sulphate and ascorbic acid mixture (ferrous ascorbate) at a dose level of 0.5 mg of iron per test. Only small amounts of radioactivity were administered, in the order of 0.1 æCi and the efficiency of the counter was such that at the 5 per cent absorption level, this could be measured with an accuracy of plus or minus 2.5 per cent of this figure. Cornmeal was given to 15 infants and an average absorption of 3 per cent of the iron was recorded compared to 24 per cent for ferrous ascorbate. In the first study in 10 infants given soybean meal, the mean absorption was 2.8 per cent but in this group the soybean meal was simply boiled and given as a porridge. In a further 9 infants the soybean porridge was baked at 300 degree F as a cake and then broken up and administered mixed with water. In this series the average absorption was 8 per cent which is more in keeping with the reported results in adults. In a further 6 infants the mean absorption of labelled haemoglobin iron was 14.4 per cent. During the course of the study it was noted that a pyrexia at the time of the absorption test was associated with a very low absorption of iron both from food and from ferrous ascorbate. Absorption measured in the same infant before or after the pyrexia was at expected levels for the iron status. Absorption was related to the haemoglobin P.C.V. and serum iron and tranferrin levels in all these infants. Iron absorption was usually but not always higher in those infants who were judged to be iron deficient(AU)

Neonatal jaundice in Jamaican children

ABO incompatibility, prematurity, maternal diabetes and Rhesus incompatibility were the only significant causes of jaundice found in 400 children born at U.H.W.I. from Jan. 4 to March 6th. Glucose-6-phosphate dehydrogenase deficiency was not found to be a significant cause (AU)

Haemoglobin concentration, eosinophilia and intestinal helminths in children in rural Jamaica

Investigations on haemoglobin and haematocrit values, eosinophils and faecal helminth eggs in rural Jamaican infants and children are summarized. Haemoglobin levels rose from 10.6g percent at about the fifth month of life to 10.9g percent at one year and thereafter climbed slowly to 12.2g percent at 6 years and remained at this level to 15 years. Values for haematocrit and MCHC behaved similarly. The mean haemoglobin levels were about 1.0g percent below optimal values but about 2.0g percent above those reported from Gambia. Severe anaemia was rare but minor degrees of iron deficiency and, in the first year of life, of folic acid deficiency, may be common. 2 cases of sickle-cell anaemia and one of thalassaemia major were seen. Neither malaria, which has been eradicated nor hookworm is now an important cause of anaemia in Jamaica. Helminth eggs in stools were not common in the first and second years but were present in 60 percent of children in the third and fourth years. Ascaris lumbricoides was the most prevalent, giving rise to the heaviest concentration of eggs, followed by Trichuris trichiura. A few hookworm eggs were found in about 10 percent of children over 2 years. In one study involving 160 children aged about 3 years, no relationship was found between helminth eggs and haemoglobin levels, heiaghts, weights or symptoms which might be related to infection. Helminthiasis, although extermely common, does not appear to be a major cause of ill-health or of failure to thrive among Jamaican children. Eosinophils were numerous in the latter half of the second year of life and by 5 years, on average, comprised 13.5 percent of all white cells. Although an aetiology other than intestinal helminthiasis in not obvious, a correlation between eosinophils and faecal helminth eggs could not be demonstrated. Some children may have been infected with Toxocara canis (Summary)

The irreversibly sickled cell: a determinant of haemolysis in sickle cell anaemia

Red cell survival was estimated in a group of adult sickle cell anaemia patients using the 51Cr technique. Counts of irreversibly sickled cells were performed on thin coverslip preparations of capillary blood. These counts are relatively constant within the same individual but show marked variations between individuals. A significant correlation has been demonstrated between the irreversibly sickled cell count and the red cell survival. This correlation does not apply to sickle cell anaemia patients with splenomegaly in whom the irreversibly sickled cell count is always low (AU)

Pregnancy and homozygous haemoglobin C disease

The effect of homozygous haemoglobin CC disease on 12 full-term pregnancies has been studied in five patients. No unusual maternal or foetal morbidity was noted. (Summary)

A comparison between the characteristics of Jamaican adults with normal hemoglobin and those with sickle cell trait

In surveys of representative samples of Jamaicans aged 35-64 years living in rural and suburan communities, no significant differences in heights, weights, hematological indices, cardiothoracic ratios, blood pressures, glycosuria, proteinuria, parity or electrocardiographic abnormalaties were apparent between 167 subjects with the sickle cell trait, AS, and 1,282 subjects with normal hemoglobin, AA. Older women with the trait had a significantly higher prevalence of bacteriuria without other evidence of urinary tract pathalogy. The findings suggest that the trait is not appreciably associated with chronic disease. (AU)

Haematological levels in Jamaican infants

A longitudinal study of 300 infants from birth to 1 year of age was carried out in Kingston, Jamaica. Haemoglobin levels were estimated 7 times during the year and serum iron and total iron binding capacity once. Hb electrophoresis was performed. In singleton children with Hb genotype AA, AS, or AC, and of birthweight 2.5kg or over, Hb levels were low after 3 months of age. These low levels were associated with iron deficiency, which was probably due to poor iron stores at birth followed by poor iron intake or absorption. It was not possible to determine whether folic acid deficiency or protein deficiency was also important. Hb levels varied with age, socioeconomic class, birthweight, sex, and rate of weight gain. The growth and health of 4 girls with homozygous sickle cell disease is mentioned.(AU)

The metabolism of iron-dextran given as a total-dose infusion to iron deficient Jamaican subjects

The movements of iron-dextran, following a total dose infusion of up to 2550 mg. iron in six severely iron deficient patients, have been studied using a Fe tagged complex. The preparation is removed from the plasma in 8-10 days. Fifty per cent of the iron was incorporated into haemoglobin in 3-4 weeks and the iron stores replenished rapidly. Using organ scanning, the liver was confirmed as the site of primary plasma clearance, but accumulations of iron were detected in the spleen and bone marrow. Only minute quantities of radioactivity appeared in the urine. No untoward effects on iron metabolism have been detected, but reduction of the serum iron and total binding capacity to low levels 6 weeks post infusion is of interest. An attempt has been made to interpret the findings to elucidate the ferrokinetics of this method of treatment.(Summary)