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Biomedical subjects

S C Davies

Publications and source records attributed to S C Davies.

At least 19 recordsLinked to original sources
PubMed1997

Blood transfusion in sickle cell disease.

Blood transfusion can be life-saving in sickle cell disease. There is an increasing body of literature available to help define its place in this patient population. In this review, we have brought together the reported trials, case reports and our experience to discuss the role of transfusion now and in the future for sickle cell disease. Advances are continually being made in all fields and we have in addition. considered the relevant ones from immunohaematology, virology and clinical medicine so that their impact on the subject is taken into consideration.

Anemia, Sickle Cell↗
PubMed1997

Alteration of an intersubunit contact in hemoglobin variants: comparative study of modifications at position alpha 126 Asp (H9).

Four human hemoglobin variants have already been described at position alpha 126 (H9), which is normally occupied by an aspartate: Hb Montefiore (-->Tyr), Hb Tarrant (-->Asn), Hb Fukutomi (-->Val), Hb Sassari (-->His). An additional variant, Hb West One (alpha 126 (H9) Asp-->Gly) is herein described. Aspartate alpha 126 (H9) is involved in a set of hydrogen bonds and salt bridges located at the C-terminal portion of the alpha-chains and of the C-helix of the beta-chains, which are broken in the oxy conformer, providing one of the most important sources of the difference in free energy between the T- and R-state in hemoglobin. A comparative study of four of these alpha 126 Hb variants is presented. An identical degree of alteration of the oxygen binding properties (increased oxygen affinity and decreased cooperativity) was found in all cases, when measured under standard experimental conditions (pH 7.2, 0.1 M NaCl). In contrast, the effect of L345 (a derivative of bezafibrate, which is a specific alpha-chain binding effector) on oxygen binding to Hb differed from one variant to another. When a bulky Tyr or His residue occupied the alpha 126 (H9) position, little effect of L345 was observed. Conversely, when this position was occupied by a residue of smaller size (Gly or Asn), normal heterotropic effects were observed. Molecular graphic modelling indicates that two classes of three-dimensional structure modifications may occur.

Allosteric Site↗
PubMed1997

Splenic regrowth in sickle cell anaemia following hypertransfusion.

We describe five adult patients with sickle cell anaemia (SS) who developed clinical, radiological and histological evidence of splenic regrowth while receiving regular blood transfusions. Five patients, all homozygous SS, range 23-34 years, were commenced on hypertransfusion therapy. Three patients were transfused because of severe recurrent vaso-occlusive crises, one for chronic sickle lung and one in an attempt to prevent deterioration of renal function. The mean duration of hypertransfusion prior to documentation of splenic regrowth was 52 months (range 12-97 months). Two patients developed significant hypersplenism. One patient had clinically-apparent splenomegaly and four patients had splenomegaly documented on ultrasound. Splenic regrowth in hypertransfused adults with sickle cell anaemia is not infrequent and may have important clinical implications.

Adult↗
PubMed1997

Collaborative multicenter investigation of marrow transplantation for sickle cell disease: current results and future directions.

We present updated results of a multicenter collaborative investigation of bone marrow transplantation for sickle cell disease. Between September 1991 and April 1997, thirty-four children less than 16 years of age with severe sickle cell disease received marrow allografts from HLA-identical siblings. Indications for transplantation included a history of stroke (n = 17), recurrent acute chest syndrome or sickle pulmonary disease (n = 10), and recurrent vaso-occlusive crises (n = 7). Twenty-one patients received regular red blood cell (RBC) transfusions to prevent complications of sickle cell disease. Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin or CAMPATH (Cambridge Pathology) antibody. Thirty-two of the 34 patients survived, with a median follow-up of 26.5 months (range, 0.2-66.9 months); and 28 patients demonstrated stable engraftment of donor hematopoietic cells. Graft rejection or recurrence of sickle cell disease occurred in four patients, and two patients died of intracranial hemorrhage or graft-vs.-host disease. In the group of 34 children with symptoms of advanced sickle cell disease, current Kaplan-Meier estimates of survival and event-free survival are 93% and 79%, respectively.

Adolescent↗
PubMed1996

Bone marrow transplantation for sickle cell disease.

BACKGROUND: We investigated the risks and benefits of allogeneic bone marrow transplantation in children with complications of sickle cell disease. METHODS: Twenty-two children less than 16 years of age who had symptomatic sickle cell disease received marrow allografts from HLA-identical siblings between September 1991 and April 1995. The indications for transplantation included a history of stroke (n = 12), recurrent acute chest syndrome (n = 5), and recurrent painful crises (n = 5). Patients were prepared for transplantation with busulfan, cyclophosphamide, and antithymocyte globulin. RESULTS: Twenty of the 22 patients survived, with a median follow-up of 23.9 months (range, 10.1 to 51.0), and 16 patients had stable engraftment of donor hematopoietic cells. In three patients the graft was rejected and sickle cell disease recurred; in a fourth patient graft rejection was accompanied by marrow aplasia. In 1 of the 16 patients with engraftment, there was stable mixed chimerism. Two patients died of central nervous system hemorrhage or graft-versus-host disease. Kaplan-Meier estimates of survival and event-free survival at four years were 91 percent and 73 percent, respectively. Among patients with a history of acute chest syndrome, lung function stabilized; among patients with prior central nervous system vasculopathy who had engraftment, stabilization of cerebrovascular disease was documented by magnetic resonance imaging. CONCLUSIONS: Allogeneic stem-cell transplantation can be curative in young patients with symptomatic sickle cell disease.

Adolescent↗
PubMed1996

Blood transfusion in sickle cell disease.

Blood transfusion can be life saving in sickle cell disease, both in emergencies and to prevent organ damage. Practice has developed through anecdote and experience so that patients are probably overexposed to transfusions in the developed world, whereas the majority of patients who live in the underdeveloped world do not have access to transfusion and those who do are exposed to unsafe practices. The role of transfusion medicine in sickle cell disease is also increasing with the development of bone marrow and solid organ transplant programs and placental stem cell banking. The modes and roles of transfusion in sickle cell disease as well as pharmacologic therapies are discussed. Multicenter, collaborative, randomized trials need to be developed, over the next few years, to study all aspects of transfusion in sickle cell disease.

Anemia, Sickle Cell↗
PubMed1996

Pain, quality of life, and coping in sickle cell disease.

This study examined the frequency and severity of sickle related pain, its impact on quality of life, and methods of coping for 25 children with sickle cell disease, aged 6-16 years. Subjects were matched with non-affected peers and asked to complete the Central Middlesex Hospital Children's Health Diary for four weeks. Results indicated that sickle pain occurred on average one in 14 days, and total summary pain scores indicated significantly greater pain than for controls. Children with sickle cell disease could discriminate sickle pain and did not adopt sick role responses to ordinary childhood ailments. Nearly all sickle pain was dealt with at home. Sickle pain resulted in over seven times increased risk of not attending school and was highly disruptive of social and recreational activities. Careful assessment of sickle pain in the home environment is an essential part of a community focused pain management service, which effectively supports children's resilience and improves their quality of life.

Activities of Daily Living↗
PubMed1996

Hb Uxbridge [beta 20 (B2)Val-->Gly]: a new variant with mild increase in oxygen affinity found during a neonatal screening program.

Hb Uxbridge [beta 20(B2)Val-->Gly] was found in an English family during a neonatal hemoglobinopathy screening program. In both the child and the parent carrying this hemoglobin variant, the red cell parameters were normal. By isoelectrofocusing Hb Uxbridge appeared to have an isoelectric point slightly higher than Hb A but was silent on cellulose acetate and acid gel electrophoresis. Structural modifications affecting position beta 20(B2) have been demonstrated to be responsible for a high oxygen affinity and polycythemia in Hb Olympia (Val-->Met) and Hb Trölhattan (Val-->Glu). In the case of Hb Uxbridge, despite an alteration of the same site, the oxygen binding parameters of the patient's hemolysate showed only a mild (ca. 20%) increase in oxygen affinity.

Female↗
PubMed1996

Barriers to bone marrow transplantation for sickle cell anemia.

While allogeneic marrow transplantation is curative therapy for patients with sickle cell anemia, only a small fraction of patients in the United States receive this treatment. We surveyed participants in our multicenter study of marrow transplantation for sickle cell anemia to determine reasons for not proceeding to transplantation. Among the 4848 patients less than 16 years of age with sickle cell anemia that were followed in 22 collaborating centers, 315 (6.5%) patients were reported to meet protocol entry criteria for transplantation, although there was wide variation among the institutions (0.9-36%). Among the 315 patients eligible for transplantation, 128 (41%) had human leukocyte antigen (HLA) typing performed, and of these 44 (14% of those meeting entry criteria) had an HLA-identical sibling. Common reasons for not proceeding with HLA typing in the remaining 187 patients included lack of a candidate sibling donor (76 patients, 24% of those meeting criteria) and lack of financial or psychosocial support (33, 10.5%). Parental refusal (30, 9.5%), physician refusal (13, 4%), history of medical noncompliance (2, < 1%), and other reasons (33, 10.5%) were less frequently cited. To date, 25 patients have been transplanted. Of the remaining 19 patients with HLA-matched donors, seven did not proceed to transplantation because of parental refusal, while the others anticipate a future transplantation (6), have experienced symptomatic improvement (4), or have relocated abroad (2). We conclude that the major barrier to marrow transplantation for sickle cell anemia is lack of an HLA-identical donor. But since only 6.5% of all children with sickle cell disease were considered eligible for transplantation, it is possible that other significant obstacles remain to be identified. For patients reported to meet eligibility criteria, parental refusal and limited financial or psychosocial support were infrequent barriers to transplantation.

Anemia, Sickle Cell↗