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S H Embury

Publications and source records attributed to S H Embury.

At least 55 records · Page 3Linked to original sources
PubMed1985

The leftward deletion alpha-thal-2 haplotype in a black subject with hemoglobin SS.

We have identified a black individual with homozygous sickle cell anemia who is the silent carrier of alpha-thalassemia (genotype - alpha/alpha alpha) due to heterozygosity for the leftward deletion alpha-thal-2 haplotype. This deletion has not been described previously in a black subject and is the only leftward deletion that we have found among 255 alpha-thal-2 chromosomes from sickle cell subjects. Its effects on the clinical, hematologic, biosynthetic, and cellular pathology of sickle cell anemia resemble those reported for the common alpha-thalassemia genotypes of the black population.

Adult↗
PubMed1985

Monovalent cation changes in sickle erythrocytes: a direct reflection of alpha-globin gene number.

It has been suggested that the less severe anemia that exists in patients with sickle cell anemia who also have alpha-thalassemia is related to an effect on the sickling of erythrocytes. To test this hypothesis, we used as a measure of sickling the change in sickle erythrocyte sodium and potassium content that occurs during deoxygenation. Sickle cells from individuals with four, three, or two alpha-globin genes were deoxygenated, and the change in monovalent cation content measured to determine whether a relationship exists between alpha-globin gene number and sickling. In samples of cells depleted of irreversibly sickled cells, the alpha-globin gene number was directly related to the magnitude of mean cation change and inversely related to the ratio of membrane surface area to cell volume. These data indicate that alpha-thalassemia is associated with a diminished degree of sickling in individuals with sickle cell anemia. They also suggest that excess cell membrane may play a role in this protective effect.

Anemia, Sickle Cell↗
PubMed1984

Effects of oxygen inhalation on endogenous erythropoietin kinetics, erythropoiesis, and properties of blood cells in sickle-cell anemia.

The role of oxygen therapy in sickle-cell anemia is not established, and its effects on erythropoiesis and on the rheologic properties of sickled erythrocytes are controversial. When three patients with sickle-cell anemia who were not in crisis or infected breathed oxygen at a rate of 5 liters per minute continuously through nasal prongs for five days, there was a rapid decline in erythropoietin levels that had initially been elevated, a delayed fall in the number of reticulocytes, and a fall in the number of irreversibly sickled cells, which, in two of the subjects, preceded the suppression of reticulocytosis. After cessation of oxygen therapy, erythropoietin levels and the number of irreversibly sickled cells increased promptly, followed by an increase in the number of reticulocytes. Calculated erythropoietin half-lives were 1.51 to 2.92 hours, and clearances were 43 to 84 ml per minute during oxygen administration. These are normal values. In two subjects, the number of irreversibly sickled cells rose to exceed base-line values after oxygen therapy was discontinued, and both subjects had acute painful episodes at this time. We conclude that in patients with sickle-cell anemia, substantial changes in erythropoiesis and in the rheologic properties of blood occur in association with oxygen inhalation and that when oxygen therapy is administered to such patients, it should be given intermittently rather than continuously.

Anemia, Sickle Cell↗
PubMed1984

Concurrent sickle cell anemia and alpha-thalassemia. Effect on pathological properties of sickle erythrocytes.

The concurrence of sickle cell anemia and alpha-thalassemia results in less severe hemolytic anemia apparently as a result of reduced intraerythrocytic concentration of hemoglobin S and its retarded polymerization. We have evaluated the effect of alpha-globin gene number on several interrelated properties of sickle erythrocytes (RBC) that are expected to correlate with the hemolytic and rheologic consequences of sickle cell disease. The irreversibly sickled cell number, proportion of very dense sickle RBC, and diminished deformability of sickle RBC each varied directly with alpha-globin gene number. Sickle RBC density was a direct function of the mean corpuscular hemoglobin concentration (MCHC). Even in nonsickle RBC, alpha-globin gene number varied directly with RBC density. Despite differences in alpha-globin gene number, sickle RBC of the same density had the same degree of deformability and dehydration. These data indicate that the fundamental effect of alpha-thalassemia is to inhibit the generation of sickle RBC having high density and MCHC, and that the other beneficial effects of sickle RBC are secondary to this process. The less consistent effect on overall clinical severity reported for subjects with this concurrence may reflect an undefined detrimental effect of alpha-thalassemia, possibly on the whole blood viscosity or on sickle RBC membrane-mediated adherence phenomena.

Anemia, Sickle Cell↗
PubMed1984

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. We minimized the role of artifact by assay of fresh samples from 84 SS individuals, including both members of 38 sib pairs. In 78 of the 84 subjects, serial values for percent F reticulocytes fell within 99.9% confidence limits or were alike by t test (P greater than or equal to .05). This left 32 sib pairs for which F reticulocyte levels in each member were reproducible. When sib-sib comparisons were limited to these 32 pairs, percentages of F reticulocytes were grossly dissimilar within 12 Jamaican and 3 American sibships. Within them, the probability that sibs were alike was always less than or equal to .005 and usually less than or equal to 10(-4). We next minimized the contribution of half-sibs among Jamaicans by a combination of paternity testing and sib-sib comparison of beta-globin region DNA restriction fragment length polymorphisms, especially among discordant pairs. We thereafter concluded that at least seven to eight Jamaican pairs were composed of reproducibly discordant full sibs. There is thus little doubt that there are genes regulating between-patient differences in F cell production that are separate from the beta-globin gene cluster. Still unanswered is (1) whether or not these genes are actually linked to beta S, (2) why F reticulocyte levels in Americans tend to be lower than in Jamaicans, and (3) whether or not differences in F cell production among SS patients are regulated by several major loci or by only one.

Adolescent↗
PubMed1983

Anemia and hemoglobinopathies in Southeast Asian refugee children.

Hematologic evaluations of 254 Southeast Asian refugee children from 163 families are reported. Hemoglobin E trait was common in Cambodians (19%) and Laotians (18%), but rare in Vietnamese (1%). beta-Thalassemia trait was most prevalent in Vietnamese (8%), and less common in Cambodians and Laotians (3%). alpha-Thalassemia was prevalent in all three groups. Hemoglobin concentrations and mean corpuscular volumes seen with hemoglobinopathies were compared with those of Southeast Asian children with normal hemoglobin. Both Hb AE and Hb EE were shown to be benign conditions resulting in microcytosis and mild, if any, anemia. In children with Hb AE, mean corpuscular volume ranged from 64 to 78 ft and Hb E from 27% to 34%. In those with Hb EE, microcytosis was more marked (50 to 63 ft). In 15 children with Hb EE, there was a delayed fall in fetal hemoglobin, which can cause diagnostic difficulties in infants.

Adolescent↗
PubMed1983

Clomiphene-responsive hypogonadism in sickle cell anemia.

Two 19-year-old men with sickle cell anemia and hypogonadism had hypothalamic dysfunction that responded to oral clomiphene therapy. The patients had no nutritional deficiencies or anatomic lesions known to result in the hypogonadism associated with sickle cell anemia. Their sickle cell disease was characterized by infrequent crises, severe hemolytic anemia, urinary iron loss, and iron deficiency. Partial hypothalamic hypogonadism was shown by low levels of testosterone, low to low-normal levels of luteinizing hormone and follicle-stimulating hormone, and a nearly normal rise in gonadotropin levels in response to exogenous gonadotropin releasing hormone. Treatment with oral clomiphene raised luteinizing hormone, follicle-stimulating hormone, and testosterone levels to normal, and induced puberty in both patients. Treatment was discontinued in one patient because of the onset of priapism, but was continued for 10 months without side effects in the other. Severe hypogonadism in patients with sickle cell anemia should be thoroughly evaluated and clomiphene therapy considered in patients with hypothalamic dysfunction.

Adult↗
PubMed1982

Concurrent sickle-cell anemia and alpha-thalassemia: effect on severity of anemia.

We studied 47 patients with sickle-cell anemia to determine the effect of alpha-thalassemia on the severity of their hemolytic anemia. We diagnosed alpha-thalassemia objectively by using alpha-globin-gene mapping to detect alpha-globin-gene deletions, studying 25 subjects with the normal four alpha-globin-genes, 18 with three, and four with two. The mean hemoglobin, hematocrit, and absolute reticulocyte levels (+/- S.D.) were 7.9 +/- 0.9 g per deciliter (4.9 +/- 0.6 mmol per liter), 22.9 +/- 2.9 per cent, and 501,000 +/- 126,000 per cubic millimeter, respectively, in the non-thalassemic group; 9.8 +/- 1.6 g per deciliter (6.1 +/- 1.0 mmol per liter), 29.0 +/- 5.0 per cent, and 361,000 +/- 51,000 per cubic millimeter in the group with three alpha-globin genes; and 9.2 +/- 1.0 g per deciliter (5.7 +/- 0.6 mmol per liter), 27.5 +/- 3.0 per cent, and 100,000 +/- 15,000 per cubic millimeter in the group with two alpha-globin genes. Deletion of alpha-globin genes was also accompanied by a decreased mean corpuscular hemoglobin concentration (MCHC) in post-reticulocyte erythrocytes and by increased hemoglobin F levels. The decreased intraerythrocytic hemoglobin S concentration and elevated hemoglobin F levels associated with alpha-thalassemia appear to diminish the degree of hemolytic anemia found in sickle-cell disease.

Adolescent↗
PubMed1982

A simple laboratory alternative to irreversibly sickled cell (ISC) counts.

Irreversibly sickled cells (ISC) are considered to be a hallmark of sickle cell disease, yet their number in peripheral blood smears varies greatly among different homozygous SS patients. This variation has suggested a role for ISC in the varying clinical manifestations of the disease. Efforts to determine the role of ISC have been complicated by the difficulty in standardizing the quantification of these cells. For this reason, we have attempted to develop an alternative method of quantification that would be less variable than the microscopic counting of cells on blood smears. Because ISC are dehydrated dense cells, a measurement based on cell density seemed an attractive alternative approach. Analysis of whole blood samples on a simple, 2-step density gradient, spun in a microhematocrit centrifuge, showed a strong correlation between the proportion of high density cells and the percentage of morphologically identified ISC. Parallel ektacytometric measurements of cell deformability, another parameter that reflects the low water content and high MCHC of ISC, were also strongly correlated with ISC counts. These findings suggest that either of these measurements, sensitive to the special physical properties of ISC, could be used as an objective substitute for the microscopic counting of ISC.

Anemia, Sickle Cell↗
PubMed1981

Risk of altitude exposure in sickle cell disease.

The risk of altitude-induced hypoxemia causing painful crisis was determined in a group of 45 predominantly adult patients with sickle cell disease. The patients were divided into two groups: those with hemoglobin (Hb) SS and those with Hb SC or Hb S beta-thalassemia. Altitude exposures were divided into airplane travel and mountain visits, and the latter subdivided into stays at 4,400 or 6,320 ft. The average risk of crisis was higher for both groups while in the mountains (37.9 percent and 56.6 percent, respectively) than it was during airplane travel (10.8 percent and 13.5 percent, respectively). The latter group had more splenic crises than the former group and also had a greater risk at 6,320 ft (65.9 percent) than at 4,400 ft (20.0 percent). Patients with sickle cell disease are at high risk of crisis in the mountains, and we advise those with intact spleens to breathe supplemental oxygen during air travel.

Adolescent↗
PubMed1980

Triplicated alpha-globin loci in humans.

We have identified 12 individuals who are heterozygous for a chromosome with three alpha-globin genes. We determined the presence of the third alpha-globin locus by restriction endonuclease digestion and hybridization with alpha-globin cDNA probes. The three alpha-globin loci resided in an elongated fragment on digestion with EcoRI, BamHI, and Xba I, and the third locus was present in an additional 3.7-kilobase fragment on digestion with Hpa I, Sac I, and Bgl II. The locations of the restriction sites are compatible with a nonhomologous crossover mechanism producing the triple alpha loci. The frequency of the triple alpha loci was 0.0036 in American blacks and less than 0.004 in Sardinians, but was higher in Greek Crypriots (0.05). Individuals with five alpha-globin genes (alpha alpha/alpha alpha alpha) apparently showed no clinical or hematologic abnormalities.

Black People↗
PubMed1980

Two different molecular organizations account for the single alpha-globin gene of the alpha-thalassemia-2 genotype.

The alpha-thalassemia-2 (alpha-thal-2) genotype or mild alpha-thalassemia gene consists of a single structural alpha-globin gene on the chromosome that normally bears two alpha-globin genes. We used blot hybridization to investigate variation in the molecular organization of this genotype and to determine the distributions of these variations in the world population. Two different patterns of gene organization responsible for the alpha-thal-2 genotype were found: the first was the result of a 4.2-kilobase pair deletion involving the normal 5' alpha-globin gene (leftward deletion alpha-thal-2 genotype), and the second probably the result of a crossover deletion of a DNA fragment bridging the two normal alpha-globin genes (rightward deletion alpha-thal-2- genotype). The rightward deletion was found in all 9 Black subjects, all 8 Mediterranean subjects, and 4 of 13 Chinese subjects. The leftward deletion was found in four and the nondeletion alpha-thalassemia lesion was found in five of the nine remaining Chinese subjects. It is likely that these deletions are related to specific DNA sequences that determine DNA recombinational events.

Asian People↗
PubMed1979

Organization of the alpha-globin genes in the Chinese alpha-thalassemia syndromes.

The alpha-thalassemia syndromes are a group of inherited anemias, the clinical severity of which has been shown to increase with the number of alpha-globin structural genes deleted. Employing restriction endonuclease gene mapping, we defined the organization of the alpha-globin genes in cellular DNA from Chinese subjects with various alpha-thalassemia syndromes. The four alpha-globin genes of normals are at two loci located on a 23.0-kilobase pair (kb) Eco RI fragment. In deletion type hemoglobin-H disease the 5' alpha-globin locus is deleted and the single 3' alpha-globin locus is found on a 19.0-kb Eco RI fragment. In alpha-thalassemia-2 there are two alpha-globin genes on a 23.0-kb Eco RI fragment and one on a 19.0-kb fragment. In alpha-thalassemia-1 and the nondeletion type of hemoglobin-H disease the two alpha-globin genes are at two loci on one chromosome and none reside on the other chromosome.

China↗
PubMed1977

Remission maintenance therapy in acute myelogenous leukemia.

Because no conclusive evidence as to the efficacy of maintenance chemotherapy in acute myelogenous leukemia (AML) existed, a study to obtain such information was done. Twenty-six adult patients with AML in whom complete remission had been achieved following induction chemotherapy were randomly assigned to receive either maintenance chemotherapy consisting of cytarabine and 6-thioguanine for two days each month or to receive no maintenance therapy. The data showed a significant difference in remission duration between the two groups, with median remission lengths for the maintained and unmaintained groups being 10.3 and 6.7 months, respectively (p<.05). In 46 percent of the maintained patients there were remissions lasting longer than 11 months, whereas in none of the unmaintained patients was there such a prolonged remission. No significant drug-induced toxicity was observed. That the prolonged exposure to these chemotherapeutic agents, which were also used in our induction program, did not adversely affect the rate of successful reinduction therapy was shown by identical 50 percent complete remission rates for second inductions in both groups. In patients with palpable splenomegaly at the time of diagnosis, there was no prolongation of remission with maintenance therapy. These data indicate the potential utility of maintenance chemotherapy for prolonging remission duration in acute myelogenous leukemia.

Adolescent↗