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D R Powars

Publications and source records attributed to D R Powars.

At least 37 records · Page 2Linked to original sources
PubMed1991

Beta s-gene-cluster haplotypes in sickle cell anemia. Clinical and hematologic features.

Identification of the beta s-gene-cluster haplotype and alpha-gene status provides a useful tool for the detection of the high-risk SS patient. The DNA polymorphisms of the beta s-gene-cluster modulate the clinical course in sickle cell anemia, especially as it involves the risk of end stage organ failure of the kidney, lung, brain, eyes, bones, and leg ulcers. This is schematically represented in Figure 4. The disease severity is modified according to the beta s-gene-cluster haplotypes and the co-inheritance of alpha-thalassemia-2. In both Africa and America, the CAR beta s haplotype increases the risk of developing an irreversible complication at an early age. The rate of progression of organ damage is regulated by the beta s-cluster haplotype from birth. The preservation of G gamma Hb F is haplotype dependent and correlates with the overall clinical course of the patient. Further modulation of the clinical course with the co-inheritance of alpha-thalassemia-2 tends to decrease the risk of soft-tissue organ failure and increase the risk of osteonecrosis. Epidemiologic studies in Africa together with clinical correlative analysis in Southern California show that SS patients with a Ben haplotype have a less severe illness than those with a CAR and a more severe illness than those with a Sen. A single individual can be expected to fit into the overall pattern. Some sickle related illness will eventually occur in all. The variable clinical manifestations in sickle cell anemia are modified according to the interaction of alpha gene deletions and the beta s-gene-cluster haplotype, are distinct for each organ, and markedly influence the age of onset of end stage major organ failure. In the presence of a Senegal haplotype, the patient's health is better; with the CAR haplotype, it is always worse; severity is intermediate in the Benin haplotype.

Africa↗
PubMed1991

Sickle cell anemia: beta s-gene-cluster haplotypes as prognostic indicators of vital organ failure.

Identification of the beta s-gene-cluster haplotype and alpha-gene status provide a useful tool to improve the possibility for early detection in high-risk SS patients. The DNA polymorphisms of the beta s-gene-cluster modify the clinical course in sickle cell anemia especially as it involves the risk of end-stage organ failure of the kidney, lung, and brain. In both Africa and America, the CAR beta s haplotype increases the risk of developing irreversible complications at an early age. The degree of anemia, the Hb F concentration, and the preservation (or lack thereof) of G gamma Hb F is haplotype dependent and correlates with the overall clinical course of the patient. Further modulation of the clinical course by the coinheritance of alpha-thalassemia-2 tends to decrease the risk of soft tissue organ failure but increases the risk of osteonecrosis. A single individual can be expected to fit into the overall pattern. Some sickle related illness will eventually occur in all patients. In the presence of a Senegal haplotype, the patient's health is better, with the CAR haplotype it is always worse; severity is intermediate in the Benin. These genetic markers can be used to identify the endangered patient before the onset of irreversible major organ failure. The high risk SS patient with a CAR chromosome or one who is homozygous Ben without alpha-thalassemia-2 should be monitored closely for evidence of vasculopathy-induced microinfarction of the brain, kidneys, or lungs. Such a patient needs preventive therapy before suffering a major hemisphere stroke, losing kidney function, or developing cor pulmonale secondary to restrictive lung disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Beta S-gene-cluster haplotypes in sickle cell anemia: clinical implications.

Restriction endonuclease analysis was used to detect alpha-gene deletions and to determine the haplotypes in the DNA of the beta S-gene-cluster [Benin, Central African Republic (CAR), and Senegal] in 221 patients with sickle cell anemia (SS). The clinical expression of SS was modified by the beta S-gene-cluster polymorphisms and the alpha-gene status (alpha-thalassemia-2). The overall risk of soft tissue organ failure caused by the obliterative sickle vasculopathy (including stroke, renal failure, chronic lung disease with cor pulmonale, leg ulcers, and young adult death) was increased threefold in those with a CAR haplotype and was decreased in those with a Senegalese chromosome (p = 0.003). In the presence of a Senegalese haplotype, the patient's health is better, and with the CAR haplotype it is always worse. With the Benin, it is intermediate. Acute recurrent clinical events including hospitalized sickle cell crisis, bone infarction, and infection are decreased in frequency in those with a Senegalese haplotype. The risk of most acute events including acute chest syndrome is equivalent in those with Benin or CAR haplotypes. In the United States, alpha-thalassemia-2 is co-inherited randomly among the beta S-gene-cluster haplotypes. Acute events occurring during childhood are minimally effected by this co-inheritance. The risk of soft tissue organ failure is decreased. After the age of 20 years, painful episodes of the lumbar dorsal area are increased in patients who had alpha-thalassemia-2 in association with degenerative bone disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗
PubMed1990

Sickle cell disease. Summer camp. Experience of a 22-year community-supported program.

A summer camp for children with sickle cell disease (SCD) and other hemoglobinopathies has been in operation for 22 consecutive years (1,556 camper weeks). Two thirds of the campers had sickle cell anemia (SS). With the exception of 1 year, SCD-related medical problems occurred in 10 percent of the children. Episodes of illness were increased during the year when the camp was held at a site 2,200 feet above sea level. Children with SCD can enjoy a remote, physically challenging, and emotionally enriching program. Success requires an experienced and prepared medical staff who leave the organization and "on site" management of camp activities to expert recreational professionals.

Adolescent↗
PubMed1990

Sickle cell anemia and major organ failure.

Major organ failure in sickle cell anemia is the direct consequence of the sickle cell evoked vasculopathy. Major organ failure is first clinically apparent as autosplenectomy, then during childhood presents as cerebral infarction and atrophy, and finally culminates in young adulthood as end stage renal failure (glomerulosclerosis), sickle chronic lung disease, intracranial hemorrhage, retinopathy, disabling leg ulcers, and generalized osteonecrosis. The vascular damage begins years before the overt clinical symptoms are apparent with no pain to act as a signal. Organ damage is progressive and irreversible. The rate of progression is genetically controlled from birth. Except for the management of life-threatening infections that are associated with the non-functioning spleen, disease expression has not been altered by therapy. The focus of future clinical investigations must be the prevention of the vasculopathy and tissue damage which is induced by the sickle red cell.

Anemia, Sickle Cell↗
PubMed1989

Nonblack patients with sickle cell disease have African beta S gene cluster haplotypes.

Of 18 nonblack patients with sickle cell disease, 14 had sickle cell anemia, 2 had hemoglobin SC disease, and 2 had hemoglobin S-beta o-thalassemia. The beta s gene cluster haplotypes that were determined in 7 patients were of African origin and were identified as Central African Republic, Central African Republic minor II, Benin, and Senegal. The haplotype Central African Republic minor II was present on the beta o-thalassemia chromosome in 2 patients. None of 10 patients whose alpha-gene status was determined had alpha-thalassemia-2. These data strongly support the concept that the beta s gene on chromosome 11 of these individuals is of African origin and that the alpha-gene locus on chromosome 16 is of white or native American origin. The clinical severity of the disease in these nonblack patients is appropriate to their haplotype without alpha-thalassemia-2 and is comparable with that of black patients. All persons with congenital hemolytic anemia should be examined for the presence of sickle cell disease regardless of physical appearance or ethnic background.

Adult↗
PubMed1989

The influence of fetal hemoglobin on the clinical expression of sickle cell anemia.

The variable levels of HbF in sickle cell anemia reflect the heterogeneous genetic mix of the beta s-gene-cluster haplotypes and coinheritance of alpha-thalassemia-2 in American SS patients. Clinical severity is less when the level of HbF reaches 20% or 1.2 g/dl or more. The coinheritance of alpha-thalassemia-2 not only increases the intracellular red cell water but modifies the HbF level in accordance with the beta-cluster haplotype. In general, the SS patient with at least one Senegalese haplotype who does not have a CAR haplotype in trans, has a significantly greater probability of maintaining HbF above 20%. This is in part related to the genetic control of the G gamma HbF locus. Such a patient is protected from arteriolar vasculopathy and subsequent major organ destruction. Much of this but perhaps not all of the better health of patients with a Senegalese haplotype can be attributed to the elevation of G gamma HbF. The coinheritance of alpha-thalassemia-2 further decreases the risk of major morbidity of the soft tissues but increases the risk of avascular necrosis of the bony skeleton. Although these heterozygous Senegal patients are healthier, eventually most, in time, will show the deleterious effect of HbS as retinopathy and avascular necrosis usually beginning after age 30 and sickle nephropathy after age 40. Because of the age-specific effect, the onset of the sickle vasculopathy is delayed by nearly 20 years in the Sen/Ben patient with increased G gamma HbF as compared to those with a CAR haplotype or the homozygous Benin. Lifetime elevation of HbF above 20% modifies the severity of disease expression and provides relative protection to the patient with sickle cell anemia.

Anemia, Sickle Cell↗
PubMed1989

Beta-cluster haplotypes, alpha-gene status, and hematological data from SS, SC, and S-beta-thalassemia patients in southern California.

The beta-gene-cluster haplotype and alpha-gene status were determined for 221 patients with sickle cell anemia, 41 with SC disease, and 21 with S-beta-thalassemia. Among SS patients, eleven beta S haplotypes were found in 21 combinations. Three haplotypes--the Benin (Ben) [---+-], the Central African Republic (CAR) [+---+], and the Senegal (Sen) [+- ]--comprise 61%, 21%, and 10% of the chromosomes, respectively. Cleavage at the Xmn I site 5' to the G gamma gene was observed only when the Senegalese arrangement was present. The linear correlation which exists between the absolute value of the G gamma chains and the Hb F for each haplotype combination suggests a feed-back mechanism which controls the G gamma to A gamma ratio and thus the Hb F level (or vice versa). The A gamma T chain was present with specific haplotypes [++-++] and [++-+-]. Heterozygous or homozygous alpha-thalassemia-2 was present in 36% of the SS patients and was randomly distributed among beta S-gene-cluster haplotypes. The variable levels of hemoglobin, MCV, Hb F, G gamma chains, and Hb A2 are in response to the heterogeneous genetic mix of the beta S-gene-cluster haplotypes and alpha-thalassemia-2 in American patients with sickle cell anemia. The influence of alpha-thalassemia-2 on the level of Hb F is dependent on the beta S-cluster haplotype. Hb A2 levels increased with decrease in the number of alpha genes. Among SC and S-beta-thalassemia patients the beta-cluster polymorphisms on the beta S chromosome were those commonly associated with the African origins of beta S haplotype. The haplotype [+--+-] was present on the C chromosome in 90% of the cases. Most beta-thalassemia chromosomes had haplotypes that matched the common African polymorphisms. An alpha-gene deletion was found in 29% of the SC and S-beta-thalassemia patients.

Adolescent↗
PubMed1987

Is sickle cell crisis a valid measure of clinical severity in sickle cell anemia?

We studied the conditional probability of developing a sickle cell crisis in 509 patients with sickle cell anemia (SS), with variable number of prior crises. These SS patients were followed during different calendar eras, having diverse complications, and had entered and/or lost to follow-up at different ages. The probability of having a sickle cell crisis during the first three decades of life increases significantly with the number of prior crises episodes (p less than 0.001). After more than five cryptogenic crises, the patient has developed a patterned response to stress that overshadows other influences, such as the effects of therapeutic agents, thus lessening the 'power' of sickle crisis as a measure of morbidity.

Age Factors↗
PubMed1986

Pregnancy in sickle cell disease.

Risks associated with pregnancy for mothers with sickle cell disease and their infants have decreased markedly during the last decade. Among 79 women with sickle cell anemia (156 pregnancies), maternal death decreased from 4.1% before 1972 to 1.7% after 1972; their infants' fetal and perinatal death rates decreased from 52.7 to 22.7% (P less than .05), and from 33.3 to 27.3% among infants of women with sickle hemoglobin C disease. There has been a significant improvement in birth weight specific mortality and an increase in number of weeks' gestation from 34.7 to 37.4 (P less than .05). A higher percentage of sickle hemoglobin C disease mothers completed their pregnancies with no complications (43%) when compared with sickle cell anemia mothers (21%), thus identifying a subset of women for whom pregnancy does not represent an increased risk. These results are attributed to improvements in state-of-the-art medical, obstetric, and perinatal care.

Adult↗
PubMed1985

Hb Aztec or alpha 2 76 (EF5) Met----Thr beta 2 detection of a silent mutant by high performance liquid chromatography.

High performance liquid chromatography has detected 14 abnormal hematological states in 600 randomly selected samples of blood. Two of these are silent mutations which are not apparent from chromatographic or electrophoretic examination. One of these has the substitution alpha 76 (EF5) Met----Thr and has been named Hb Aztec. The variant was first detected in a 9-day-old baby girl who had inherited it from her mother. This abnormal hemoglobin has no obviously deleterious effect on hematological status or health.

Adolescent↗
PubMed1984

Is there a threshold level of fetal hemoglobin that ameliorates morbidity in sickle cell anemia?

When the clinical manifestations of 272 patients with sickle cell anemia are compared with their level of fetal hemoglobin (HbF), the results suggest that there may be a threshold above which HbF is effective in ameliorating the morbidity of this disease. The age of entry of these SS patients into the study ranged from birth to 56 yr; the average length of follow-up was 11 yr for a total of 3,011 patient-years of clinic observation. HbF was determined quantitatively by microchromatographic procedures; the mean for HbF was 10% +/- 6% with a range from 2% to 32%. For major organ failure, analyzed as termination events of morbidity, such as stroke or aseptic necrosis, the threshold appears to be 10%, whereas for recurrent clinical events, such as crisis or pulmonary disorders, it is 20%. No linear trend was found between HbF levels and morbidity. If a threshold exists, it is important to recognize this fact when attempts are made to raise the level of HbF in patients with sickle cell disease.

Adolescent↗
PubMed1983

Small noncleaved follicular center cell (FCC) lymphoma: Burkitt and non-Burkitt variants in the United States. I. Clinical features.

With the understanding that Burkitt's lymphoma was of follicular center cell (FCC) derivation, Lukes and Collins classified the tumor, descriptively, as small noncleaved FCC lymphoma. Two subtypes were described: Burkitt and non-Burkitt. Attempting to define the clinicopathologic features of the subtypes, we studied 42 patients: 25 Burkitt and 17 non-Burkitt. Histologically, the Burkitt tumor demonstrated remarkable uniformity of nuclear size and contour, whereas the non-Burkitt variant had greater variability. Immunoglobulin monoclonality was demonstrated in 83% of Burkitt and 81% of non-Burkitt cases. Burkitt patients tended to be younger. Gastrointestinal disease was seen in 15 Burkitt and only four non-Burkitt patients (P less than 0.05). Disseminated disease was found in the majority of both variants. Marrow involvement was demonstrated in 4.5% of Burkitt and 37.5% of non-Burkitt patients (P less than 0.05). Median survival of Burkitt patients was 10.5 months versus 7.7 months in the non-Burkitt group. The authors believe that significant biologic differences between the variants have been demonstrated, which may be of potential value to the clinician.

Adolescent↗
PubMed1981

Acquired methemoglobinemia.

Cases of acquired methemoglobinemia have been identified with increasing frequency in Los Angeles during the last several years. Among 18 patients, both infants and adults, the most commonly incriminated agent was silver nitrate used for topical antibacterial prophylaxis of burn wounds. One burned child died from overwhelming septicemia complicated by hypoxia with a methemoglobin level of 5.4 grams per dl. Other causative factors included nitrate-rich vegetables used in early infancy, additives in ethnic foods, and prescribed and overdosed drugs. Discontinuation of the precipitating agent and methylene blue therapy were usually followed by prompt improvement. In burned patients treated with silver nitrate, careful regular monitoring of serum methemoglobin levels and early initiation of specific therapy are mandatory.

Adolescent↗
PubMed1981

Negative charge distribution and density on the surface of oxygenated normal and sickle red cells.

Negative charges on the external surface of red cells were visualized by colloidal iron hydroxide labelling of 50% of the membrane area after osmotic hemolysis and glutaraldehyde fixation. Counts were made over randomly selected areas on electron micrographs at 350,000 x magnification. Statistical analyses showed that at the 95% level of confidence there was no significant difference between oxygenated normal (AA) and sickle (SS) cells in either the distribution or the density of negative charges.

Anemia, Sickle Cell↗