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Biomedical subjects

L J Benjamin

Publications and source records attributed to L J Benjamin.

17 recordsLinked to original sources
PubMed2000

Sickle cell anemia day hospital: an approach for the management of uncomplicated painful crises.

Painful crisis episodes are poorly treated in sickle cell anemia, both in timeliness and appropriateness of care. Delayed treatment in Emergency Departments, unrelieved pain, frequent admissions, and prolonged hospitalizations are common. We established a Day Hospital (DH) to determine if an alternative care delivery system could improve pain relief and reduce unnecessary hospital admissions for patients with uncomplicated painful crises. Trained DH staff delivered prompt titration for pain relief based on each patient's analgesic history and qualitative and quantitative assessments. Response to therapy and comorbidities commanded disposition. During the first 5 years of DH operation there were 2554 visits; 60% of the patients had severe pain. During an average visit of 4.5 hours, 84% of the patients were titrated to relief; 90% had pain relief within 2 to 4 hours. Overall, 81% of the patients were discharged home (70% initially and 90% to 94% in the last 3 years). During the first 5 years of the DH, there were 2612 emergency department (ED) visits that averaged 13 hours each. The combined ED and DH admissions during this time represented a 40% decrease in the baseline ED admission rate of 92%, (1 year pre-DH). Patients with uncomplicated painful crisis were admitted 5 times less often from the DH (8.3%) than from the ED (42.7%). The length of stay (LOS) for inpatients followed by the DH staff decreased by 1.5 days, while the LOS for patients followed by non-DH staff remained unchanged. Reduction of admissions and LOS represented a savings of approximately $1.7 million. We conclude that a dedicated facility provides the kingpin for effective and rapid painful crisis management, reduces hospitalizations, and facilitates integration of the approach into other areas of care. (Blood. 2000;95:1130-1136)

Adult↗
PubMed2000

Gibberellins in seedlings and flowering trees of Prunus avium L.

Extracts of acids from mature seeds, germinating seeds, first, second and third year seedlings as well as mature, flowering trees of sweet cherry (Prunus avium L. cv. Stella) were analysed by gas chromatography-mass spectrometry. The presence of the known gibberellins (GAs) GA1 (1), GA3 (4), GA5 (7), GA8 (11), GA19 (14), GA20 (12), GA29 (13), GA32 (5), GA85 (2), GA86 (3) and GA87 (6) was confirmed by comparison of their mass spectra and Kovats retention indices with those of standards or literature values. In addition, 16alpha,17-dihydrodihydroxy GA25 (16) was identified and its stereochemistry confirmed by rational synthesis. The 12alpha,13-dihydroxy GAs, GA32 (5), GA86 (2), GA86 (3) and GA87 (6), were detected in mature seeds, germinating seeds and young seedlings, but not in flowering plants. The 13-hydroxy GAs, GA1 (1) and GA3 (4), were present in germinating seeds and, in addition to these, GA5 (7), GA8 (11), GA19 (14), GA20 (12) and GA29 (13) were detected in seedlings and mature flowering plants. In germinating seeds and seedlings (while the plants were growing actively), concentrations of the 12alpha,13-dihydroxy GAs, measured by bioassay, declined and those of the 13-hydroxy GAs increased. The results are discussed with reference to the known and predicted effects of the GAs on the vegetative growth and flowering of P. avium plants.

Chromatography, High Pressure Liquid↗
PubMed1999

Accuracy of pulse oximetry in sickle cell disease.

Pulmonary complications and hypoxemia are common in sickle cell disease (SCD) and may exacerbate microvascular occlusive phenomena. Thus, detecting hypoxemia is of particular importance in SCD. To assess the accuracy of pulse oximetry in the diagnosis of hypoxemia in SCD, we compared 22 pulse oximetric measurements of arterial oxygen saturation (SpO2) in adult patients with SCD and acute vasoocclusive crisis with simultaneously drawn arterial saturation (SaO2 = oxyhemoglobin divided by oxyhemoglobin plus reduced hemoglobin) measured by co-oximetry. We accepted SpO2 readings only if they were stable and characterized by strong and regular photoplethysmographic waves on the oximeter screen. To assess the position of these patients' oxyhemoglobin dissociation curves, we plotted arterial and venous oxygen saturation (SaO2 and SvO2 ) against oxygen tension. We found right-shifted oxyhemoglobin dissociation curves, with pH-corrected p50s ranging from 28 to 38 mm Hg. Pulse oximetry slightly overestimated oxyhemoglobin percentage (by an average of 3.4 percentage points), but it almost always accurately estimated SaO2 (underestimating on average by 1.1 percentage points). The error in SpO2 was never enough to classify a hypoxemic patient erroneously as normoxemic or a normoxemic patient as hypoxemic. We conclude that, as long as strong and regular photoplethysmographic waves are present, pulse oximeters can be relied upon not to misdiagnose either hypoxemia or normoxemia in SCD.

Acute Disease↗
PubMed1997

Sickle cell-related pain: perceptions of medical practitioners.

Pain is the most common problem encountered by patients with sickle cell disease (SCD). We report the results of a survey sent to hematologists and emergency department (ED) physicians regarding their perceptions and practices concerning pain and its management. Hematologists and ED physicians differed considerably in their perceptions about the natural history of the pain, and about the percentage of patients who are addicted to analgesics. Fifty-three percent of the ED physicians and 23% of the hematologists thought that more than 20% of patients are addicted. These beliefs and perceptions about SCD-related pain and the prevalence of addiction must be addressed if clinical care is to be changed substantively.

Anemia, Sickle Cell↗
PubMed1994

Classification of red blood cells as normal, sickle, or other abnormal, using a single image analysis feature.

Sickle cell anemia is a disease for which there is currently no effective treatment. One method of evaluating clinical status is the counting of cell types based on morphology. There is a need for a rapid, reproducible method, superior to human inspection, for classification of these cells. Quantitative digital-image analysis is being applied to this need. Blood from 24 patients with sickle cell anemia (SS) and SC disease and ten hematologically normal volunteers (AA) was stressed by bubbling with nitrogen. One hundred fifty cells were analyzed from each sickle specimen, and 100 were analyzed from each nonsickle specimen. Expert observers classified each cell as normal (N), sickle (S), or other abnormal (A). Cells were analyzed with a custom, high-resolution image-analysis instrument. A total of 42 features including metric, optical density-derived, and textural features were extracted. The metric feature Form Factor (4 pi Area/Perimeter2) was selected by recursive partitioning analysis as the sole feature needed for segregating cells into the classes of N, A, and S. The agreement of automated classification (using cutpoints determined by recursive partitioning analysis) with a human expert for specimens from individuals with sickle cell anemia was 89% for N-, 73% for A-, and 92% for S-classified cells. For specimens from AA individuals, the agreement was 92% for N and 76% for A. For specimens from individuals with sickle cell anemia, rates of agreement between two human experts were compared and found to be 86% for N, 84% for A, and 80% for S. For specimens from AA individuals, the agreement was 90% for N and 87% for A.

Adolescent↗
PubMed1994

Textural differences between AA and SS blood specimens as detected by image analysis.

High-resolution image analysis was employed in the analysis of round (discoid) erythrocytes from hematologically normal (AA) individuals, AA individuals with nonspecific anemia, individuals with sickle cell trait (AS), individuals with SC disease (SC), and individuals with sickle cell anemia (SS). The shape feature Form Factor (4 pi Area/Perimeter2) was used to select round cells and to exclude sickle and other abnormal cells. Textural features extracted from round cells of SS and SC patients were found to differ from those derived from cells of normal andanemic AA individuals. Two textural features, Standard Deviation of Run Length Matrix Counts and Rotation Moment of the Cooccurrence Matrix, discriminated between patients mean values from AA samples and those from SS samples. The ability of textural features to separate round cells into classes based on genotype suggests that high resolution image analysis may be an effective tool in the study and monitoring of sickle cell disease.

Adolescent↗
PubMed1993

Biochemical and functional properties of recombinant human sickle hemoglobin expressed in yeast.

Previous studies had indicated that recombinant and natural human sickle hemoglobin had similar chemical properties (Martin de Llano, J. J., Schneewind, O., Stetler, G., and Manning, J. M. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 918-922). In the present study, additional biochemical and physiological characterization of some primary through quaternary structural features of recombinant sickle hemoglobin are described. The molecular weight of the purified recombinant sickle hemoglobin was identical to natural sickle hemoglobin as determined by mass spectrometry, thus excluding extensive post-translational modification in the yeast system. Carboxypeptidases A and B together catalyzed the release of COOH-terminal amino acids at the same rate for recombinant and natural hemoglobin S, consistent with identity in their primary and secondary structures in this region of the molecule. The tryptic peptide maps of natural and recombinant hemoglobins were practically indistinguishable, indicating the same internal protein sequences for recombinant and natural hemoglobins. As a probe of the secondary structure of recombinant sickle Hb, the reactivity of the SH group of Cys-93(beta) was investigated for the glutathione sickle hemoglobin adduct, which has significant anti-gelling and anti-sickling properties. The position of glutathione at Cys-93(beta) was established by direct mass spectrometric analysis of enzyme digests; reduction of this derivative to the unmodified chains was also observed by mass spectrometry and by isoelectric focusing. The oxygen equilibrium curves of recombinant and natural sickle hemoglobin at high protein concentration were superimposable with identical Hill coefficients of 3.3. The response of recombinant sickle hemoglobin to chloride with respect to a lowered oxygen affinity was identical to that of natural sickle hemoglobin. The gelation properties of recombinant and natural sickle hemoglobins were identical at the high hemoglobin concentrations that occur in the red cell. Therefore, the yeast expression system synthesizes a completely functional recombinant sickle hemoglobin with the same biochemical and physiological properties as natural sickle hemoglobin with respect to features characteristic of its primary through quaternary structures.

Amino Acids↗
PubMed1992

Effects of methyl acetyl phosphate, a covalent antisickling agent, on the density profiles of sickle erythrocytes.

Methyl acetyl phosphate specifically acetylates valine-1, lysine-82, and lysine-144 in the 2,3-diphosphoglycerate binding cleft of hemoglobin S, thereby inhibiting its gelation (greater than 32 gm/dl) at pH 7.4. To extend these findings, the effect of methyl acetyl phosphate on the density of sickle cells has been evaluated by phthalate ester gradient centrifugation and by Larex-Percoll density centrifugation. After treatment with methyl acetyl phosphate (40% modification of the intracellular hemoglobin S), oxygenated sickle erythrocytes had a lowered density profile, as measured in a phthalate ester gradient. Thus 83% of untreated oxygenated sickle cells had densities greater than 1.098 gm/ml, whereas after treatment with methyl acetyl phosphate, 52% of the cells were in this density range. Under anaerobic conditions, methyl acetyl phosphate was even more effective in lowering cell density. For example, 50% of untreated deoxygenated cells had densities greater than 1.098 gm/ml, but none of the cells treated with methyl acetyl phosphate were this dense. For studies with Larex-Percoll density gradients, sickle erythrocytes were first separated into two fractions (densities greater than and less than 1.1 gm/ml) by Percoll-Hypaque centrifugation. The amount of oxygenated sickle cells exhibiting densities greater than 1.074 gm/ml decreased by about 32% on treatment with methyl acetyl phosphate. For deoxygenated sickle cells, treatment with methyl acetyl phosphate resulted in an average decrease of approximately 24% in the number of cells with densities greater than 1.074 gm/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia, Sickle Cell↗
PubMed1991

Single-unit transfusions of RBC enzymatically converted from group B to group O to A and O normal volunteers.

Full-unit transfusions of RBC enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBC) to group O and A normal healthy individuals exhibit excellent in vivo survival times (24-hour survival 95.1% +/- 2.3%, T50 36.9 +/- 4.6 days). These results confirm our earlier findings describing ECO RBC in vitro viability and normal in vivo survival time after small-volume infusions. No significant increase in pretransfusion anti-B titer or score is observed in either group O or A subjects provided that sufficient enzyme is used to treat the cells: Cells transfused to group O recipients require higher levels of enzyme (185 to 200 U/mL RBC) than those infused to group A (90 U/mL RBC). Two separate single-unit transfusions of ECO RBC to one group O recipient (4.5 months apart) also survived normally (24-hour survival 96% and 92%, T50 40 and 36 days) and did not increase preexisting anti-B levels in this subject. ECO RBC were not agglutinated or lysed by recipient sera before or after transfusion. Similarly, no antibody development to the alpha-galactosidase used in cell treatment (and washed from the product before transfusion) could be detected in any subject. The sustained increase in hemoglobin levels after transfusion of ECO RBC suggests that this product will be useful in treatment of acute and chronic anemia.

ABO Blood-Group System↗
PubMed1987

Inhibition of the gelation of extracellular and intracellular hemoglobin S by selective acetylation with methyl acetyl phosphate.

Methyl acetyl phosphate binds to the 2,3-diphosphoglycerate (2,3-DPG) binding site of hemoglobin and selectively acetylates three amino groups at or near that site. The subsequent binding of 2,3-DPG is thus impeded. When intact sickle cells are exposed to methyl acetyl phosphate, their abnormally high density under anaerobic conditions is reduced to the density range of oxygenated, nonsickling erythrocytes. This change is probably due to a combination of direct and indirect effects induced by the specific acetylation. The direct effect is on the solubility of deoxyhemoglobin S, which is increased from 17 g/dL for unmodified hemoglobin S to 22 g/dL for acetylated hemoglobin S at pH 6.8. Acetylated hemoglobin S does not gel at pH 7.4, up to a concentration of 32 g/dL. The indirect effect could be due to the decreased binding of 2,3-DPG to deoxyhemoglobin S within the sickle erythrocyte, thus hindering the conversion of oxyhemoglobin S to the gelling form, deoxyhemoglobin S.

2,3-Diphosphoglycerate↗
PubMed1987

Effects of methyl acetyl phosphate on hemoglobin S: a novel acetylating agent directed towards the DPG binding site.

Methyl acetyl phosphate (MAP) is an acetylating agent which prevents the polymerization of sickle cell hemoglobin (HbS). MAP can penetrate sickle erythrocytes and can acetylate intracellular HbS. Tryptic peptide mapping of modified HbS on reversed phase HPLC and amino acid analysis of isolated peptides revealed the acetylation sites to be Val-1 (beta), Lys-82 (beta), and Lys-144 (beta). MAP, therefore, is specifically directed towards the 2,3-DPG binding site of Hb.

Acetylation↗
PubMed1986

A collaborative, double-blind randomized study of cetiedil citrate in sickle cell crisis.

We have recently completed a double-blind, placebo-controlled, noncrossover study, the goal of which was to determine whether cetiedil citrate (cetiedil) could affect the course of vaso-occlusive crises in sickle cell disease. Patients, who presented to the emergency room at least 4 but no more than 24 hours after the onset of a painful vasoocclusive crisis severe enough to require hospitalization, were considered candidates for the study. Each patient received either placebo or cetiedil at one of the following three dosages: 0.2, 0.3, or 0.4 mg/kg body weight. The assigned drug dosage was given as a 30 minute intravenous infusion every 8 hours for 4 consecutive days. A total of 67 patients was enrolled in the study. Cetiedil, at its highest dosage (0.4 mg/kg body weight), was found to be significantly superior to placebo both in reducing the number of painful sites present on all 4 treatment days and in shortening the total time in crisis. No serious adverse reactions were observed during the course of the study. We conclude that cetiedil, given at a dosage of 0.4 mg/kg body weight, is therapeutically advantageous for sickle cell crisis.

Adolescent↗
PubMed1986

Enhanced survival of sickle erythrocytes upon treatment with glyceraldehyde.

Glyceraldehyde has been demonstrated to be an antisickling agent in vitro. In the present investigation, chromium-51 red cell studies were used to investigate the life span in vivo of sickle erythrocytes after treatment with glyceraldehyde in vitro. The mean survival (T1/2) of control cells was 5.8 +/- 1.6 days, whereas cells treated with 10 mmol/L or 20 mmol/L glyceraldehyde survived 9.0 +/- 1.4 (P less than .05) and 11.3 +/- 0.8 (P less than .002) days, respectively. The extent of modification by glyceraldehyde was 0.4 to 1.0 lysine residue per hemoglobin tetramer. These studies demonstrate not only a prolongation of the life span of sickle erythrocytes by treatment with glyceraldehyde but also the absence of any deleterious effects that would be revealed by this study.

Adult↗
PubMed1977

Production paroxysmal nocturnal hemoglobinuria-like red blood cells by tea.

Normal human red cells incubated with saline extracts of tea develop paroxysmal nocturnal hemoglobinuria-like defects as demonstrated by positive acid and sucrose hemolysis tests. All of a variety of tea preparations tested provoked a sensitivity to complement-dependent hemolysis and, with one exception, a moderate decrease in red cell acetylcholinesterase activity. Complement-dependent hemolysis in teaincubated red cells was inhibited by antisera to C3 and C3 activator, but not by antisera to C4. This suggests that incubation with tea may alter the red cell membrane in a way that specifically potentiates the lytic effects of the alternate pathway of complement, but not the classic pathway. Leupeptin, a protease inhibitor, also prevented complement-dependent hemolysis of red cells incubated with tea. Although the clinical consequences of these observations are unknown, the study was initiated following a report of a young male who had developed an acute limited intravascular hemolytic episode following ingestion of large quantities of a herbal tea.

Acetylcholinesterase↗