PubMed Health⌕ Search

Biomedical subjects

Samir K Ballas

Publications and source records attributed to Samir K Ballas.

At least 19 recordsLinked to original sources
PubMed2007

Morbidity and mortality in chronically transfused subjects with thalassemia and sickle cell disease: A report from the multi-center study of iron overload.

A natural history study was conducted in 142 Thalassemic (Thal), 199 transfused Sickle Cell Disease (Tx-SCD, n = 199), and 64 non-Tx-SCD subjects to describe the frequency of iron-related morbidity and mortality. Subjects recruited from 31 centers in the US, Canada or the UK were similar with respect to age (overall: 25 +/- 11 years, mean +/- SD) and gender (52% female). We found that Tx-SCD subjects were hospitalized more frequently compared with Thal or non-Tx-SCD (P < 0.001). Among those hospitalized, Tx-SCD adult subjects were more likely to be unemployed compared with Thal (RR = 1.6, 95% CI 1.0-2.5) or non-Tx-SCD (RR = 3.1, 95% CI 1.3-7.3). There was a positive relationship between the severity of iron overload, assessed by serum ferritin, and the frequency of hospitalizations (r= 0.20; P = 0.009). Twenty-three deaths were reported (6 Thal, 17 Tx-SCD) in 23.5 +/- 10 months of follow-up. Within the Tx-SCD group, those who died began transfusion (25.3 vs. 12.4 years, P < 0.001) and chelation therapy later (26.8 vs. 14.2 years, P = 0.01) compared with those who survived. The unadjusted death rate in Thal was lower (2.2/100 person years) compared with that in Tx-SCD (7.0/100 person years; RR = 0.38: 95% CI 0.12-0.99). However, no difference was observed when age at death was considered. Despite improvements in therapy, death rate in this contemporary sample of transfused adult subjects with Thal or SCD is 3 times greater than the general US population. Long term follow-up of this unique cohort of subjects will be helpful in further defining the relationship of chronic, heavy iron overload to morbidity and mortality.

Adolescent↗
PubMed2006

Hydroxyurea and sickle cell anemia: effect on quality of life.

BACKGROUND: The Multicenter Study of Hydroxyurea (HU) in Sickle Cell Anemia (MSH) previously showed that daily oral HU reduces painful sickle cell (SS) crises by 50% in patients with moderate to severe disease. The morbidity associated with this disease is known to have serious negative impact on the overall quality of life(QOL) of affected individuals. METHODS: The data in this report were collected from the 299 patients enrolled in the MSH. Health quality of llife (HQOL) measures were assessed in the MSH as a secondary endpoint to determine if the clinical benefit of HU could translate into a measurable benefit perceptible to the patients. HQOL was assessed with the Profile of Mood States, the Health Status Short Form 36 (SF-36), including 4-week pain recall, and the Ladder of Life, self-administered twice 2-weeks apart pre-treatment and every 6 months during the two-year, randomized, double-blind, treatment phase. The effects of factors including randomized treatment, age, gender, pre-treatment crises frequency, Hb-F level mean, daily pain from 4-week pre-treatment diaries, and 2-year Hb-F response level (low or high) were investigated. RESULTS: Over two years of treatment, the benefit of HU treatment on QOL, other than pain scales, was limited to those patients taking HU who maintained a high HbF response, compared to those with low HbF response or on placebo. These restricted benefits occurred in social function, pain recall and general health perception. Stratification according to average daily pain prior to treatment showed that responders to HU whose average daily pain score was 5-9 (substantial pain) achieved significant reduction in the tension scale compared to the placebo group and to non-responders. HU had no apparent effect on other QOL measures. CONCLUSION: Treatment of SS with HU improves some aspects of QOL in adult patients who already suffer from moderate-to-severe SS.

Activities of Daily Living↗
PubMed2006

N-terminal pro-brain natriuretic peptide levels and risk of death in sickle cell disease.

CONTEXT: Thirty percent of patients with sickle cell disease (SCD) develop pulmonary hypertension, a major risk factor for death in this population. A validated blood biomarker of pulmonary hypertension in SCD could provide important prognostic and diagnostic information and allow the exploration of the prevalence of pulmonary hypertension in participants in the 1996 Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH) Patients' Follow-up Study. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) provide such information in patients with idiopathic pulmonary arterial hypertension. OBJECTIVE: To determine the relationship between NT-proBNP levels and severity of pulmonary hypertension and prospective mortality in patients with SCD. DESIGN, SETTING, AND PARTICIPANTS: NT-proBNP levels were measured in 230 participants in the National Institutes of Health (NIH) Sickle Cell Disease-Pulmonary Hypertension Screening Study (enrollment between February 2001 and March 2005) and in 121 samples from patients enrolled starting in 1996 in the MSH Patients' Follow-up Study. A threshold level predictive of high pulmonary artery pressure and mortality was identified in the NIH Sickle Cell Disease-Pulmonary Hypertension Screening Study and used to define an a priori analytical plan to determine the prevalence and associated mortality of pulmonary hypertension in the MSH follow-up study. MAIN OUTCOME MEASURES: Severity of pulmonary hypertension and risk of all-cause mortality. RESULTS: NT-proBNP levels were higher in patients with sickle cell pulmonary hypertension and correlated directly with tricuspid regurgitant jet velocity in the NIH cohort (R = 0.50, P<.001). An NT-proBNP level of 160 pg/mL or greater had a 78% positive predictive value for the diagnosis of pulmonary hypertension and was an independent predictor of mortality (21 deaths at 31 months' median follow-up; risk ratio, 5.1; 95% confidence interval, 2.1-12.5; P<.001; 19.5% absolute increase in risk of death). In the MSH cohort, 30% of patients had an NT-proBNP level of 160 pg/mL or greater. An NT-proBNP level of 160 pg/mL or greater in the MSH cohort was independently associated with mortality by Cox proportional hazards regression analysis (24 deaths at 47 months' median follow-up; risk ratio, 2.87; 95% confidence interval, 1.2-6.6; P = .02; 11.9% absolute increase in risk of death). CONCLUSIONS: Pulmonary hypertension, as indicated by an NT-proBNP level of 160 pg/mL or greater, was very common in patients in the NIH study and in the MSH cohort. The MSH analysis suggests that rates of vaso-occlusive pain episodes in these patients were unrelated to risk of death; this risk was largely determined by occult hemolytic anemia-associated pulmonary hypertension.

Adult↗
PubMed2006

Folate supplementation and twinning in patients with sickle cell disease.

Patients with sickle cell disease routinely take folic acid daily as a supplement to maintain effective erythropoiesis. One of the controversial effects of folic acid is its effect on twin gestation rates. In this report, we present our experience in patients with sickle cell disease and twin pregnancy. Our data show that twin pregnancies seem to be associated with folate supplementation.

Abortion, Spontaneous↗
PubMed2006

Bloodstream infections in hospitalized adults with sickle cell disease: a retrospective analysis.

Bloodstream infections (BSI) are a common cause of morbidity and mortality in people with sickle cell disease (SCD). In children with SCD, BSI are most often caused by encapsulated organisms. There is a surprising paucity of medical literature that is focused on evaluating SCD adults with BSI. We reviewed the charts of adults with SCD and BSI who were admitted to our hospital between April 1999 and August 2003. During this period a total of 1,692 hospital admissions for 193 adults with SCD were identified and 28% of these patients had at least 1 episode of positive blood cultures, with 69 episodes (17%) considered true BSI. Nosocomial BSI occurred in 34 episodes (49%). Among community BSI, in contrast to BSI in children with SCD, Streptococcus pneumoniae was rarely encountered. A high incidence of staphylococcal BSI in adults with SCD was noted. Twenty-eight percent of all BSI were caused by Staphylococcus aureus, and 15 of 22 isolates (68%) of these were methicillin-resistant. Gram-negative organisms, anaerobes, and yeast were found in 21 (27%), 3 (4%), and 4 isolates (5%) of BSI, respectively. Since over 80% of BSI were considered catheter-related, the higher incidence of gram-positive bacterial infections was likely due to the presence of indwelling central venous catheters. Empiric therapy for adults with SCD suspected of having BSI, especially in the presence of indwelling central venous catheters, should include antimicrobial therapy targeted at gram-positive bacteria (especially MRSA) and gram-negative bacteria. Also, if patients are critically ill, consideration should be made to include antifungal agents. Additional research into the adult SCD population appears necessary to further define this problem.

Adult↗
PubMed2006

Secretory phospholipase A2 levels in patients with sickle cell disease and acute chest syndrome.

In a multicenter study (eight centers), we determined secretory phospholipase A(2) (sPLA(2)) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA2 levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22-35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels > or =1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25-35 after baseline. Nine of 43 (20%) patients had baseline sPLA2 values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA(2( for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.

Acute Disease↗
PubMed2006

Hyperhemolysis during the evolution of uncomplicated acute painful episodes in patients with sickle cell anemia.

BACKGROUND: Some patients with sickle cell anemia (SS) experience significant decrease in their hemoglobin (Hb) level and significant increase in reticulocyte count during the progression of uncomplicated acute painful episodes. These changes have been attributed to, but not proven, hyperhemolysis. This study provides evidence of hyperhemolysis in this group of patients. STUDY DESIGN AND METHODS: Hospitalized patients who met the above criteria were identified and followed prospectively, and the measures of red blood cell (RBC) survival were determined. The latter included 1) laboratory measures of hemolysis: Hb level, reticulocyte count, nucleated RBC count, RBC distribution width (RDW), total bilirubin, lactate dehydrogenase (LDH), and aspartate transaminase (AST); 2) determination of RBC survival in vivo by the (51)Cr method in selected patients; and 3) the determination of the RBC Hb:reticulocyte Hb ratio. Baseline values of these measures were also obtained and compared to the crisis data. RESULTS: During the evolution of the painful episode in the selected patients, there was a significant increase in total bilirubin, LDH, AST, nucleated RBC count, and RDW that are indicative of hyperhemolysis. There was a significant decrease in RBC Hb:reticulocyte Hb and (51)Cr RBC survival, which is diagnostic of hyperhemolysis. CONCLUSION: Together, the data indicate that hyperhemolysis occurs during uncomplicated acute painful episodes in some patients with SS. The presence of free plasma Hb, consequent to hyperhemolysis, reduces nitric oxide bioavailability, promotes endothelial dysfunction, and contributes to the development of pulmonary hypertension and vasoocclusion.

Anemia, Sickle Cell↗
PubMed2006

Utilization of the office, hospital and emergency department for adult sickle cell patients: a five-year study.

Sickle cell disease (SCD) is a hematological disorder that is manifested primarily by severe pain and chronic organ damage. Little normative data exists on what the usual healthcare utilization is of a population of SCD patients, especially adults. Our study analyzed the office, emergency department (ED) and hospital use data for 142 patients who received care for three consecutive years. Relationships between health service use, patient age, gender and sickle cell phenotype were described. Multivariate analyses studied relationships between demographic and clinical characteristics and levels of office, independent ED and inpatient encounters over a five-year period (1997-2001). We found female patients were older and had less ED and hospital admissions. The 20% highest inpatient utilizers accounted for 54% of the ED total visits, 52% of the ED independent visits, 54% of hospital bed days and 24% of office visits. The ED was a common place for utilization, with a mean of 7.4 visits per patient year, a third of which resulted in a hospital admission. The healthcare utilization of our adult sickle cell population is very complex, with a subset of our patients accounting for a majority of the resources used and female patients living longer but with less ED and hospital admissions.

Adult↗
PubMed2005

Hospital readmission for adult acute sickle cell painful episodes: frequency, etiology, and prognostic significance.

The acute sickle cell painful episode is the most common cause of hospitalization of patients with sickle cell anemia. Its detailed clinical features and peri-discharge features are not well known. In order to determine the actual pattern of hospital admissions of patients with SS and the causes of frequent hospital readmissions and their prognostic significance, we conducted a prospective longitudinal and observation cohort study of all adult patients with sickle cell anemia admitted to Thomas Jefferson University Hospital between January 1998 and December 2002. Major outcome measures included the frequency, etiology, and prognostic significance of readmissions to the hospital within 1 week and 1 month after discharge. Incidence of mortality among patients during the study period was also determined. Analysis of the data showed that about 50% of hospital admissions for acute painful episodes were readmitted within 1 month after discharge, and about 16% of all admissions were within 1 week after discharge. The intensity of pain score decreased significantly during the first 4 days of hospital admission (P < 0.001) and then reached a plateau until discharge. The mean score of pain intensity was >7 throughout the hospital stay. Causes of hospital readmission included premature discharge, withdrawal syndrome, and recurrence of new acute episodes. Readmission within 1 week after discharge was associated with higher mortality than otherwise. This study shows that hospital readmission of adult patients with sickle cell anemia is common. It suggests that improvement is needed in the management of pain during hospitalization and at home after discharge. Patients who are readmitted frequently within 1 week of discharge have poor prognosis and require careful monitoring.

Adult↗
PubMed2005

Blood samples collected under venous oxygen pressure from patients with sickle cell disease contain a significant number of a new type of reversibly sickled cells: constancy of the percentage of sickled cells in individual patients during steady state.

We found various levels of a new type of reversibly sickled cell (RSC) with blunt edges in 44 blood samples obtained from 32 steady-state patients with sickle cell disease (SCD) without exposure to air (UnExp-blood). Because these RSCs could be generated in vitro by partial oxygenation of once-deoxygenated SS cells to venous oxygen pressure, we named them "partially oxygenated sickled cells" (POSCs). These RSCs were classified into elongated and non-elongated RSCs, depending on the ratio of the short axis to long axis. The presence of these cells was previously unknown because the standard blood collection method oxygenates most of the POSCs to discocytes due to oxygen in the air space in the needle, syringe, and blood collection tube (Exp-blood). Although the shape of elongated POSCs is similar to that of irreversibly sickled cells (ISCs), POSCs revert to discocytes upon exposure to air. We found the following: (1) the percentage of total sickled cells (total POSCs + ISCs) in UnExp-blood (29.0 +/- 14.5%) was significantly higher than the percentage of sickled cells (mainly ISCs) in Exp-blood (7.3 +/- 5.7%); (2) the percentage of sickled cells in UnExp-blood was specific to individual patients during steady state, while it decreased at the onset of a vaso-occlusive event; and (3) the percentage of sickled cells in UnExp-blood varied widely among steady-state patients (4-56%). This new type of RSC may be used as an internal biomarker to evaluate the disease state of individual patients.

Adolescent↗
PubMed2005

Pain management of sickle cell disease.

Management of sickle cell disease continues to be primarily palliative, including supportive, symptomatic, and preventive approaches to therapy. There are three major types of sickle cell pain: acute, chronic, and neuropathic pain. The acute painful episode is the insignia of the disease and the most common cause of hospitalization. Its management entails the use of nonpharmacologic and pharmacologic modalities. Pain management should follow certain principles that include an assessment stage, treatment stage, reassessment stage, and adjustment stage. Chronic sickle cell pain may be due to certain complications of the disease, such as leg ulcers and avascular necrosis; intractable chronic pain may be due to central sensitization. Management of chronic pain should take a multidisciplinary approach.

Acute Disease↗
PubMed2004

Aggregation of normal and sickle hemoglobin in high concentration phosphate buffer.

Sickle cell disease is caused by a mutant form of hemoglobin, hemoglobin S, that polymerizes under hypoxic conditions. The extent and mechanism of polymerization are thus the subject of many studies of the pathophysiology of the disease and potential treatment strategies. To facilitate such studies, a model system using high concentration phosphate buffer (1.5 M-1.8 M) has been developed. To properly interpret results from studies using this model it is important to understand the similarities and differences in hemoglobin S polymerization in the model compared to polymerization under physiological conditions. In this article, we show that hemoglobin S and normal adult hemoglobin, hemoglobin A, aggregate in high concentration phosphate buffer even when the concentration of hemoglobin is below the solubility defined for polymerization. This phenomenon was not observed using 0.05 M phosphate buffer or in another model system we studied that uses dextran to enhance polymerization. We have used static light scattering, dynamic light scattering, and differential interference contrast microscopy to confirm aggregation of deoxygenated and oxygenated hemoglobins below their solubility and have shown that this aggregation is not observable using turbidity measurements, a common technique for assessing polymerization. We have also shown that the aggregation increases with increasing temperature in the range of 15 degrees -37 degrees C and that it increases as the concentration of phosphate increases. These studies contribute to the working knowledge of how to properly apply studies of hemoglobin S polymerization that are conducted using the high phosphate model.

Buffers↗
PubMed2004

Management of acute chest wall sickle cell pain with nebulized morphine.

This paper describes, for the first time, the utilization of nebulized morphine in the management of severe chest pain in two young adult African-American patients who suffered from generalized acute sickle cell painful episodes. While hospitalized, both patients developed new sharp chest wall pain, and were treated with nebulized morphine started at 20 mg MOSO4 in 3.0- to 5.0-mL physiologic buffered saline solution. Within minutes, both patients reported significant relief of chest wall pain. Patient 1 achieved 90% pain relief as well as a significant decrease in the pain intensity score. Patient 2 reported 40% pain relief, and the pain intensity score decreased to a mean of 5.6/10. Hence, treatment every 6 hr was continued for 10 days, after which the chest wall pain subsided. These findings indicate that nebulized morphine may prove effective in the management of acute chest pain in patients with sickle cell anemia. This is a desirable alternative in patients with difficult venous access and may more specifically target chest pain.

Administration, Inhalation↗
PubMed2004

Non-pharmacologic management of sickle cell pain.

Patients with sickle cell disease (SCD) suffer from both acute and chronic pain. The latter includes avascular necrosis of the hip joints mostly in the adult population. It has a negative impact on the quality of life of affected individuals and is often associated with depression, disability, unemployment and dependence on opioid analgesics. In this study, we show that a non-pharmacologic approach to management with deep tissue/deep pressure massage therapy technique, including neuromuscular trigger point treatment with acupressure, in patients with SCD has a salutary effect on pain relief and quality of life.

Activities of Daily Living↗
PubMed2004

Sickle red cell microrheology and sickle blood rheology.

The hallmark of the phenotypic expression of sickle cell disease is the remarkable degree of heterogeneity in the clinical manifestations. They vary latitudinally among patients and longitudinally in the same patient. The pathogenesis of sickle cell anemia centers on the sequence of events that occur between polymerization of deoxy hemoglobin S and increased red cell destruction, vasoocclusion, and end organ damage. Cellular dehydration, changes in sickle red blood cell rheology, adhesion of sickle red cells to vascular endothelium, inflammatory response, and tissue injury are some of the factors that contribute to hemolytic anemia, vasoocclusion, and eventual multiorgan damage. The focus of this review is on the rheology of sickle blood and microrheology of sickle RBC. Determinants of sickle RBC rheology and the factors that modulate its severity are discussed.

Anemia, Sickle Cell↗
PubMed2004

Safety of purified poloxamer 188 in sickle cell disease: phase I study of a non-ionic surfactant in the management of acute chest syndrome.

Acute chest syndrome (ACS) is the most common cause of death in patients with sickle cell anemia. Its management is primarily palliative. We performed a Phase I evaluation of purified poloxamer 188 (a non-ionic surfactant) in the management of ACS. Forty-three patients with sickle cell disease and ACS were treated with doses as high as 2960 mg/day by continuous intravenous (IV) infusion. The maximum tolerated dose has not been identified. No evidence of renal toxicity or other limiting adverse events were found. One adult patient died due to sepsis and adult respiratory distress syndrome, which were unrelated to treatment. Poloxamer 188 is safe to administer to patients with ACS, and preliminary data suggest that it may shorten its duration and the length of hospitalization in a dose related manner. Children appeared to benefit more than adults. The data and safety profile justify further studies with purified poloxamer 188 in the treatment of ACS.

Adolescent↗
PubMed2003

Hydroxyurea analogues as kinetic and mechanistic probes of the nitric oxide producing reactions of hydroxyurea and oxyhemoglobin.

Derivatives of N-hydroxyurea that contain an N-hydroxy group react with oxyhemoglobin to form methemoglobin and variable amounts of nitrite/nitrate. Compounds with an unsubstituted -NHOH group produce the most nitrite/nitrate, which provides evidence for nitric oxide formation. The rate of reaction of these N-hydroxyurea derivatives with oxyhemoglobin correlates well with that compound's oxidation potential. Aromatic N-hydroxyureas react 25-80-fold faster with oxyhemoglobin than with N-hydroxyurea, suggesting other N-hydroxyurea analogues may be superior nitric oxide donors. Electron paramagnetic resonance spectroscopy shows that the formation of a low-spin methemoglobin-hydroxyurea complex is critical for iron nitrosyl hemoglobin formation. These results show that iron nitrosyl hemoglobin formation from the reaction of hydroxyureas and hemoglobin requires an unsubstituted -NHOH group and that the nitrogen atom of the non-N-hydroxy group must contain at least a single hydrogen atom. These results should guide the development of new hydroxyurea-based nitric oxide donors and sickle cell disease therapies.

Electrochemistry↗