Day-to-day variation in iron-status indexes in elderly women.

Day-to-day variability in biochemical indicators of iron status in well-hydrated and healthy women 70-79 y old (n = 10) was determined. Venous blood was collected on 4 nonconsecutive days during a 2-wk period. Analytical (sigma 2 rep) and biological (sigma 2 fd) variance components were computed based on a previously established scheme in younger adults. These two variance components were summed to obtain the total day-to-day variability (sigma 2 fd). Our results indicate that biological variation contributed most to the intraindividual variation. We calculated that sampling once for most iron indexes and twice for plasma transferrin receptors in elderly individuals is adequate to accurately determine these indexes whereas serum iron and transferrin saturation, indexes with high CVfd, require seven and eight measurements, respectively. These data, compared with previously published data in younger adults, demonstrate that aging is associated with a decreased variation in some indexes of iron status such as serum ferritin.

Iron deficiency and anemia of chronic disease in elderly women: a discriminant-analysis approach for differentiation.

To differentiate iron-deficiency anemia and anemia associated with chronic inflammatory diseases in elderly women, subsets of laboratory, dietary, and functional assessment variables were obtained by using discriminant analysis. Fifty-one subjects (70-79 y of age) were classified into one of four groups on the basis of the presence of iron deficiency and chronic inflammatory disease. Iron deficiency was defined on the basis of a significant response in hemoglobin concentration after iron supplementation. The discriminating subset of laboratory tests consisted of measures for serum ferritin, plasma transferrin receptors, and erythrocyte sedimentation rate. The discriminant function classified subjects into iron-deficient, anemia of chronic disease, or a category in which the two coexist, with an error rate of 18.6%. The addition of other variables (dietary iron and functional assessment information) did not appreciably improve the classification. The results of these three key laboratory tests may help to identify functional iron deficiency in the presence of chronic inflammation.

Hypertension following erythropoietin therapy in anemic hemodialysis patients.

Recombinant human erythropoietin (rHuEpo) corrects the anemia of end-stage renal disease. However, hypertension has been observed as an adverse effect of increasing red cell mass. In our study, 44 of 63 patients (70%) treated with rHuEpo had an increase in mean arterial pressure greater than 10 mm Hg or required new or additional hypertensive medications. Retrospective analysis disclosed that increasing blood pressure was associated with pretreatment hematocrit level less than or equal to 0.20 (P = .05) and dependency on red cell transfusions (P less than .01). Factors not associated with hypertension included the rate of rise of the hematocrit, the net rise in hematocrit, age, sex, the number of years on dialysis, the presence or absence of kidneys, smoking, or the presence of pretreatment hypertension. Noninvasive hemodynamic studies in eight normotensive patients before and after improvement of the anemia demonstrated a normalization of the decreased peripheral vascular resistance and a reduction toward normal in the elevated cardiac output. In three of these patients, clinical hypertension subsequently evolved. Follow-up hemodynamic studies in nine other patients receiving new or additional antihypertensive medications were difficult to interpret. Although the hypertension can be controlled with routine medication, hypertensive encephalopathy may occur if the blood pressure increases rapidly when the hematocrit increases with rHuEpo therapy.

Day-to-day variation in iron status indexes is similar for most measures in elderly women with and without rheumatoid arthritis.

OBJECTIVE: To determine the day-to-day variation in biochemical measures of iron status in a group of elderly women with rheumatoid arthritis compared with a group of healthy elderly women. DESIGN: Venous blood samples were collected from each subject on 3 nonconsecutive days during a 2-week study period; subjects had fasted overnight. Variability in hemoglobin level, hematocrit value, serum iron concentration, total iron-binding capacity, transferrin saturation, serum ferritin concentration, and plasma transferrin receptor level was determined. SUBJECTS: Two groups of women, one with rheumatoid arthritis (n=10) and another that was apparently healthy (n=10). STATISTICAL ANALYSES: Variance component analysis was used to estimate the biological variation (sigma square day) and analytic variation (sigma square rep) for each iron index. The coefficient of variation (CV) for each variance component was calculated: coefficient of biological variation = CV day, coefficient of analytic variation = CV rep, and coefficient of a single future determination = CV fd. RESULTS: The CV rep for all iron indexes was smaller than the CV day in both groups. The CV day was considerably higher for serum iron concentration and for transferrin saturation than for the other indexes in both groups (16.6% and 16.6% in healthy subjects and 33.6% and 28.2%, respectively, in subjects with rheumatoid arthritis). The higher CV day for serum iron concentration and transferrin saturation translated into a higher CV fd for these indexes. Because of the higher variance for these two indexes, more sampling days were required for reliable estimates. CV day and CV fd for plasma transferrin receptor level were relatively low. CONCLUSIONS: These findings corroborate our previous finding that variation of serum ferritin concentration in the elderly is lower than that demonstrated in younger populations. This aging effect persists in the presence of rheumatoid arthritis. Fasting appeared to improve reliability in the determinations for serum iron concentration and transferrin saturation. Variability estimates for the indexes other than serum iron concentration and transferrin saturation were not altered by the inflammation of rheumatoid arthritis. Plasma transferrin receptor level is a reliable index for assessing iron status in populations with rheumatoid arthritis.

Effects of erythropoietin on strength and functional status of patients on hemodialysis.

The strength, endurance, and functional status of 15 anemic (HCT 21.2 +/- 4.6) hemodialysis patients was quantified prior to the administration of erythropoietin (epoetin) and after the anemia was partially corrected (HCT 35.4 +/- 2.3). Subjects showed significant increases in strength, measured isometrically (p < .01) and isokinetically (p < .01 at four of five speeds). They also demonstrated improved endurance and rated their functional ability higher. Anemia contributes to significant debilitation in hemodialysis patients and, when reversed with epoetin therapy, results in significantly improved muscle function and endurance.

The long-term effects of recombinant human erythropoietin on the cardiovascular system.

Fifty-five hemodialysis patients (pts) received rHuEpo for 3-5 years (51 +/- 11 months, hematocrit 32.5 +/- 3.7). BP medication was required in 42% of pts prior to rHuEpo (Hct 20.8 +/- 3.5) and 69% (38 patients) now require such therapy. BP was controlled with single therapy in 16 pts and only 8 required 3 or more different BP drugs. Vascular access clotting episodes were rare in pts with autologous fistula (17 of 24 pts had no clotting), whereas access clotting episodes were 10 times more common in pts with AV grafts, yet 20% had no clotting after 3-5 years of rHuEpo. Heart size decreased in most who initially had cardiomegaly. Cardiovascular related and other deaths were decreased in this selected group when compared to other dialysis pts matched for age, race and type of renal disease.

Further characterization of transfusion-related acute lung injury: demographics, clinical and laboratory features, and morbidity.

According to Food and Drug Administration data, transfusion-related acute lung injury (TRALI) is the third most frequent cause of transfusion-associated death in the United States and is characterized by an acute respiratory distress syndrome-like clinical picture following transfusion of plasma-containing blood components. It may be underdiagnosed due to unfamiliarity of clinicians with the syndrome. This report describes the largest series to date, 46 cases, occurring between 1992 and 1998. The male-to-female ratio was approximately 1:1. The mean age at diagnosis was 54 years. The most frequent presenting symptom or signs were acute respiratory distress, hypotension, and hypertension. Antibodies to human leukocyte antigens or granulocytes were identified in 61 percent of cases, with 50 percent associated with antibodies in a donor whose blood had been transfused to a patient developing TRALI. Clinical recovery occurred in 87 percent of patients, but TRALI contributed to deaths in 13 percent. Clinicians need to recognize and diagnose this syndrome in order to respond with appropriate interventions.

Cocaine babies: the scourge of the '90s.

Six cases of cocaine-related deaths of infants have covered the spectrum of potentially devastating effects. They include an intrauterine death of a 35-week-old fetus following acute maternal cocaine abuse; anoxic encephalopathy at birth with 3 months' vegetative survival from a similar episode; traumatic compression asphyxia in a 4-month-old; infectious cardiomyopathy with heart failure in a twin at age 21 months following maternal cocaine abuse at birth; malnutrition and dehydration in a 7-week-old during continuing cocaine abuse by the parents; and a teenage sibling's cocaine lacing of a baby milk bottle ingested by his 6-week-old brother. All the cases had positive toxicological screening for cocaine or metabolites or both in the mother at delivery or in the infant at birth, or both. There were no instances of sudden infant death syndrome (SIDS, or "crib death"). Pathologic and toxicologic, as well as birth, developmental, and social data are presented. An integrated medical, public health, law enforcement, and educational policy to prevent or at least ameliorate these tragic cases, now approaching epidemic proportions, has yet to be developed. A careful obstetrical history and examination of the mother, indication on the birth certificate of maternal drug abuse, and notification of health authorities (by birth certificate checking, among other ways) may send an early warning message to providers for intercession. Active ingestion/injection and passive inhalation by older children and teenagers require more intensive monitoring and aggressive interaction by pediatricians, social workers, school authorities, and employers.(ABSTRACT TRUNCATED AT 250 WORDS)

Modification of a commercial cell sorter to support efficient and reliable preparation of ALDH-bright cells for clinical use.

BACKGROUND: Cell populations manufactured by conventional commercial cell sorters have been safely infused into patients, but reliably sterilizing these instruments remains challenging. We are developing clinical protocols involving use of ALDH bright cells manufactured by cell sorting in patients. However, we encountered problems when we attempted to reliably sterilize the FACSAria cell sorter using standard methods. RESULTS: We have identified and modified potential sources of microbial contamination in several FACSAria systems. We added new filter systems to the sheath and sample air lines, to the wet cart fluid supply, and to the sample line. Sheath was provided from an external sterile, disposable bag through sterile disposable tubing sets. The plenum reservoirs were modified in several ways to allow efficient decontamination of internal surfaces. A new bubble filter assembly was added and one valve was eliminated from the sample pathway to improve flow cell sterilization. A new cleaning and sterilization protocol was developed and validated. All cell products manufactured using the modified instrument and validated cleaning protocol have met lot release criteria for prevention of microbial contamination and safe clinical use. DISCUSSION: The instrument modification and cleaning protocol described enable reliable manufacture of ALDH bright cell populations that are suitable for clinical trials. We have manufactured nineteen consecutive samples that meet all clinical release criteria in an on-going Phase 1 human trial.

A multistate cluster of red blood cell transfusion reactions associated with use of a leucocyte reduction filter.

In 2000, the American Red Cross (ARC) received reports of unusual transfusion reactions of unknown aetiology among patients receiving leucocyte-reduced (LR) red blood cell (RBC) units in multiple distribution regions. We evaluated potential risk factors of reactions among patients who received LR-RBC transfusions. A case-patient was defined as any patient with onset of back pain while receiving an LR-RBC transfusion from 1 January to 25 May 2000. Controls were chosen randomly and selected in a 1:3 case : control ratio from healthcare facilities in which case-patients were transfused. Product-specific risk factors of reactions were further determined through nested case-control study, procedural review of blood collection facility and quality-control-testing record review of product processing. Reaction incidence rates were determined through ARC blood product distribution data by region of blood collection and processing. There were 29 reactions detected in patients who received transfusions in 13 healthcare facilities in five states. Eighteen case-patients and 78 controls were included in the case-control study. In univariate analysis, case-patients were more likely than controls to have a haematologic malignancy, to have received the transfusion as an outpatient, to have received an RBC transfusion within the previous 3 months, to have received medication used to prevent reactions or to diminish their intensity upon transfusion (i.e. premedication) or to have received LR-RBC units prepared with the HemaSure r\LS System(HS) rather than two other filters used. In multivariate analysis limited to recipients of HS-filtered RBC units, transfusion premedication [adjusted odds ratio (AOR) = 7; 95% confidence interval (CI) 1.4-37; P = 0.02] and transfusion as an outpatient (AOR = 5; 95% CI 1.1-20; P = 0.03) were independently associated with reactions. The rate of reported transfusion reactions was 2.0 reactions per 10 000 RBC units distributed. A multistate cluster of transfusion reactions was significantly associated with leucocyte filtration of RBC units prepared with a specific product, the HS filter. The reactions also were independently associated with premedication and transfusion as an outpatient; these may be surrogates for an increased risk of reaction or for greater likelihood of detection. The mechanism for these reactions has not been elucidated. This cluster of reactions underscores the importance of surveillance efforts to detect adverse events after transfusion, particularly when new methods to modify blood products are introduced.

A comparison of the responses to recombinant human erythropoietin in normal and uremic subjects.

The erythropoietic response to graded doses of recombinant human erythropoietin (epoetin alfa) was assessed in 24 hemodialysis patients by quantitative ferrokinetic studies, and measurement of the reticulocyte count and plasma levels of transferrin receptor protein. These responses were compared to those of 22 normal subjects. Epoetin alfa was given intravenously at 15, 50 or 150 U/kg every other day for four injections. Three patients with chronic renal failure were restudied after renal function was restored following renal transplantation. The results of these three different measurements of erythroid function showed that the acute response to recombinant human erythropoietin was similar in normal subjects and patients with renal failure. We conclude that chronic uremia does not alter the responsiveness to erythropoietin in vivo.

Effectiveness of recombinant human erythropoietin therapy in myelodysplastic syndromes.

In an attempt to determine predictors of response to recombinant human erythropoietin (r-HuEPO) therapy in 20 patients with various subtypes of myelodysplastic syndrome (MDS), plasma concentrations of transferrin receptor protein were measured before and after 4 doses of r-HuEPO. An r-HuEPO dosage of 150 U/kg was administered subcutaneously 3 times weekly and increased to 300 U/kg in patients who failed to raise plasma concentrations of transferrin receptor protein by at least one third. Ten (50%) patients had an effective clinical response to therapy by reducing (greater than 50%) or eliminating transfusion requirements, or by showing an improvement in haematocrit of greater than or equal to 6 percentage points. Changes in plasma transferrin receptor protein concentrations failed to predict which patients would eventually respond to r-HuEPO therapy. A subset of MDS patients demonstrated a delayed response to therapy in order to achieve a satisfactory clinical outcome. Precise predictors of response, either laboratory or clinical, remain to be determined. Continued research is warranted in this group of patients in order to specifically target r-HuEPO therapy. It is, however, likely that r-HuEPO therapy will have an effective and important role in this subset of MDS patients.

Motor vehicle fatalities in Rhode Island (FY1990-1991): a report on driver impairment.

Autopsy specimens from 52 fatally injured drivers in Rhode Island were analyzed for the presence of alcohol and other drugs of abuse, including, among others, cocaine, opiates, cannabinoids (THC), and phencyclidine (PCP). The ages of the drivers ranged from 16 to 87 years; 41 were male and 11 female. Based on this sample, 65% of Rhode Island driver fatalities involve drugs. The most common drug, alcohol was found in 59% of the cases. Drugs other than alcohol were detected in 19% of the cases, 13% had illicit drugs found in combination with alcohol, and 6% had illicit drugs only.