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PubMed1988

Diagnostic fetal umbilical blood sampling in the management of isoimmunization.

Current management of isoimmunization in pregnancy is predicted on the assumption that all sensitized women carry antigen-positive fetuses. In addition, management is based on indirect predictors of the magnitude of the fetal hemolytic disease. We present a preliminary report using a new approach of direct fetal blood sampling for the diagnosis and treatment of these patients. This form of evaluation provides specific information about fetal red blood cell antigen status and the degree of fetal anemia at an earlier gestational age than that validated by the Liley curves and eliminates empiricism from both the diagnosis and treatment of the isoimmunized pregnancy. The use of such a management protocol reduces the need for multiple invasive procedures in fetuses at little risk for disease and provides specific information about the status of those fetuses truly at risk.

Blood Group Incompatibility↗
PubMed1988

Cordocentesis: an appraisal of risks.

Fetal blood sampling via cordocentesis is being used with increasing frequency. Between March 1986 and February 1988, we performed 58 intravascular transfusions (64 attempts) and 27 fetal blood samplings (28 attempts) guided by ultrasonography. The complication rates for intravascular transfusion and fetal blood sampling were 9.4% (6 of 64) and 7.1% (2 of 28), respectively. The procedure-related mortality rates were 4.7% (3 of 64) and 0%. We caution that the potential complications be seriously considered when appropriate patients are selected for cordocentesis. Additionally, we recommend that cordocentesis be performed only in tertiary care centers by personnel skilled in both ultrasonography and prenatal diagnosis.

Blood Specimen Collection↗
PubMed1991

Risk factors for cordocentesis and fetal intravascular transfusion.

There is little information on the impact of technical aspects or patient characteristics on the risks of accessing the fetal circulation. We performed 594 diagnostic cordocenteses and 156 intravascular transfusions over 6 years. Pancuronium was administered during 52% of procedures. The number of needle punctures per successful procedure was unrelated to the placental location. However, the number of punctures required was lower if the placental cord origin rather than a midsegment was targeted (p less than 0.0001). Bleeding from either the uterine or umbilical cord puncture site was not believed to be clinically significant, although the duration of bleeding was greater after arterial puncture than after venous puncture (p = 0.01) and after intravascular transfusion than after diagnostic cordocentesis (p less than 0.0001). Amnionitis (suspected plus verified) complicated 0.5% of procedures. Preterm premature rupture of membranes (with or without amnionitis) followed 0.4% of procedures. Fetal bradycardia occurred in 6.6% (6.6 +/- 0.8 minutes; range, 0.1 to 35 minutes). There were five perinatal losses after a diagnostic procedure, yielding an uncorrected loss rate of 0.8% (5/594). Each was associated with a prolonged bradycardia; each fetus was ultimately demonstrated to have been unsalvageable. Two independent risk factors for bradycardia were identified--arterial puncture and severe, early onset intrauterine growth retardation. The administration of pancuronium reduced the incidence of bradycardia in appropriately grown fetuses (6% to 1.5%; p less than 0.05), but did not alter the incidence in growth-retarded fetuses. We conclude that cordocentesis performed with a needle guide is a safe procedure but that its risk varies with both the indication and the vessel punctured.

Blood Specimen Collection↗
PubMed1989

The issues in autologous transfusion.

Autologous transfusion should be recognized by patients and physicians as an important measure to provide safer transfusion therapy. This should be suggested to patients in general good health (who are not obviously frail) who have no significant medical problems and no likelihood of severe reaction, who can take iron supplements, and who have at least a 10% chance of using blood during surgery or are having surgery in which the average use is one or more units. Such patients should receive iron supplementation beginning 1 week before the first autologous donation, and should donate one to five units on a weekly basis, but no more frequently than every 72 hours, with their last unit donated 72 hours before surgery. Elderly individuals may donate if the risk of donor reaction seems low. In children and adults, the amount of blood removed should be reduced in proportion to the blood volume if the individual does not meet the standard weight of 50 kg for a 450-mL donation. "Fail-safe" identification systems should be used; these will insure that the correct donor/patient receives the transfusion. Processing of the units is preferred but still optional. Use of these units as homologous units should not be done unless the donor has a hematocrit level acceptable to an autologous donor, meets all the criteria for recipient safety, the unit is processed and negative for all viral markers, and the donor has recently (eg, within 3 years) participated in the volunteer donor program. The unit should be transfused to the patient in situations in which homologous blood would be indicated. Safeguards to prevent volume overload are needed when the unit is stored as whole blood. Future research objectives should include the use of recombinant erythropoietin to prevent donation-induced anemia, delineation of medical conditions which should contraindicate the donation, and determination of the real costs involved in autologous transfusion. Education of the general public, patients, and physicians about the desirability of autologous transfusion should proceed. Third-party carriers also need to be educated about the cost implications and the need to pay for this activity. However, such education should also stress that autologous units will only cover planned, elective surgery and that major blood needs for emergency surgery, trauma, and chronic transfusion will still need to be met by homologous blood from altruistic community blood donors.

Anemia↗
PubMed1996

Safety and immunogenicity of a recombinant hepatitis B vaccine administered to infants at 2, 4 and 6 months of age. The Kaiser-UCLA Vaccine Study Group.

A recombinant hepatitis B vaccine was administered to over 5000 infants in a prospective, randomized and blinded study. Infants were given either recombinant hepatitis B vaccine (Engerix-B, SmithKline Beecham Pharmaceuticals, 10 micrograms dose-1) or a Haemophilus influenzae type b (Hib) conjugate vaccine at 2, 4 and 6 months of age simultaneously with diphtheria-tetanus-pertussis and oral polio vaccines. Adverse reactions were ascertained by parental reports and interviews, and review of medical records. Blood specimens collected from 269 infants given hepatitis B vaccine were assayed for antibody to hepatitis B surface antigen (anti-HBs) by enzyme immunoassay. Infants given hepatitis B vaccine experienced low rates of adverse reactions that were similar or lower than the rates in infants given Hib conjugate vaccine. The geometric mean anti-HBs concentrations were 9.6 mIU ml-1 after one dose, 333 mIU ml-1 after two doses and 1812 mIU ml-1 after three doses (99% had levels > or = 10 mIU ml-1). Antibody responses to diphtheria and tetanus toxoids were unaffected by simultaneous administration of hepatitis B or Hib conjugate vaccine. Engerix-B vaccine was safe and immunogenic when given with other routine childhood immunizations at 2, 4 and 6 months of age, and should provide long-term protection against hepatitis B virus infection.

Antibodies, Bacterial↗
PubMed2005

Microcirculatory hemodynamics after acute blood loss followed by fresh and banked blood transfusion.

BACKGROUND: Red blood cell (RBC) conformational changes occur when blood is stored. This study was designed to be a preliminary evaluation to assess how these changes affect the microcirculation. METHODS: The rat cremaster muscle flap model was used to evaluate in vivo microcirculatory changes after withdrawal of 1 mL blood with subsequent administration of fresh blood (group I, n=6) and banked blood (group II, n=6). Each group underwent a 3-stage evaluation: baseline, after blood withdrawal, and after transfusion. Using intravital microscopy, RBC velocity, vessel diameter, functional capillary perfusion, and leukocyte-endothelial interactions were noted. RESULTS: After blood withdrawal, changes in RBC velocity, vessel diameter, functional capillary perfusion, and number of activated leukocytes were observed in both groups, but these changes were more significant in stored blood compared with fresh blood (P<or=.05). CONCLUSIONS: Further work is needed to validate these findings, but these preliminary data suggest that stored blood may have a deleterious effect on the microcirculation.

Animals↗
PubMed2005

Detection of circulating cancer cells with K-ras oncogene using membrane array.

K-ras oncogene is frequently found in human cancers and thus may serve as a potential diagnostic marker for cancer cells in circulation. So far, there is no reliable method for detecting cancer cells with K-ras oncogene in peripheral blood. The objective of this study was to develop a diagnostic membrane array using activated K-ras oncogene-associated molecules as detection targets. In our previous study, cDNA microarray analysis showed that there were 94 genes differentially expressed in K-ras mutant stably transfected adrenocortical cells. In the present study, we obtained 22 up-regulated genes in the closest relation to K-ras oncogene through bioinformatic analysis. At first, we carried out membrane array analysis by using in vitro culture cells. We demonstrated that this diagnostic technique was feasible and highly sensitive. A number as low as 5 cancer cells bearing K-ras oncogene in 1 ml of blood could be distinctively detected. Then, we collected blood specimens from 76 cancer patients. Direct sequencing analysis of these 76 samples showed that K-ras mutation was present in 43 patients with mutation sites mainly at codons 13, 15 and 61, which have been commonly established to be activated sites. We subsequently analyzed these 76 specimens with our diagnostic membrane array. Thirty-nine specimens were detected as positive for activated K-ras oncogene. Eighty percent (12/15) of mutations occurred at codon 13, 72.7% (8/11) at codon 61, and 88.9% (8/9) at codon 15 were accurately detected by our diagnostic membrane. Finally, through a series of biostatistical analyses, the sensitivity, specificity and accuracy of the diagnostic membrane array were 83.7, 90.9 and 86.8%, respectively. These findings suggest that the K-ras oncogene membrane array has a great potential for further investigation and clinical application.

Computational Biology↗
PubMed2006

Influence of hematocrit and localisation of punch in dried blood spots on levels of amino acids and acylcarnitines measured by tandem mass spectrometry.

BACKGROUND: Detection of amino acids (AA), acylcarnitines (AC), and guanidinoacetate (GAA) in dried blood spots by tandem mass spectrometry has made it possible to detect different inborn errors of metabolism in neonatal screening programs. Despite its proven sensitivity many issues related to sample preparation remain unsolved. Hematocrit has a profound effect on blood viscosity, and may thereby influence flux and diffusion properties of the blood. As newborn infants show a considerable interindividual variability of hematocrit levels, we investigated its effect on levels of AA and AC in dried blood spots. METHODS: Blood samples with defined hematocrit levels (20%, 30%, 40%, 50%, 60%) were produced by diluting blood cells with plasma from a single donor. Forty dried blood spots were made for each hematocrit level and a central as well as a peripheral 3 mm disk was punched and analysed for AA, AC, and GAA, respectively. RESULTS: Levels of most AA and GAA increased significantly with increasing hematocrit (p<0.001), while the effect of hematocrit on some AA was less pronounced. Total AC, free carnitine, some long, medium and short chain AC correlated positively with hematocrit levels (p<0.001). In samples with low hematocrit, levels of most AA and free carnitine were higher in the peripheral than in the central disk (p<0.0001). CONCLUSIONS: Both hematocrit and position of the disk within the dried blood spot have a significant and sometimes additive effect on levels of AA, AC and GAA in dried blood spots. Theoretically, diagnoses may be missed depending on hematocrit and position of the disk.

Amino Acids↗
PubMed2005

Effect of anemia on plasma concentrations of NT-proBNP.

BACKGROUND: Concentrations of the amino-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) are increased in the blood of patients with heart failure. Understanding the variables that influence the concentrations of NT-proBNP is required to refine its clinical use criteria. The effect of anemia on plasma concentrations of NT-proBNP was investigated. METHODS: Hemoglobin and NT-proBNP were measured in blood specimens collected from 209 adult patients without heart failure or renal disease. RESULTS: The median NT-proBNP concentration of patients with anemia was significantly higher than in those without anemia (82 vs. 232 ng/l, p<0.0001). Anemic patients were also 3 times more likely to have an NT-proBNP concentration that exceeded age-specific cutoffs recommended by the assay manufacturer (odds ratio 3.1, 95% CI 1.7 to 5.4, p<0.0001). CONCLUSIONS: Decreased concentrations of hemoglobin are sufficient to produce serum concentrations of NT-proBNP above diagnostic cutoffs in anemic patients without heart failure independent of gender, body mass index, glomerular filtration rate, left ventricular hypertrophy, and valve disease. The impact of this finding on the clinical use and interpretation of the test needs to be examined.

Adolescent↗
PubMed2005

Low HDL cholesterol is associated with suicide attempt among young healthy women: the Third National Health and Nutrition Examination Survey.

BACKGROUND: Serum cholesterol is reported to be associated with suicidality, but studies conducted among general healthy population are rare. We examined the association between serum cholesterol and suicidality in a national sample of the general population of US. METHODS: We used the data of 3237 adults aged 17 to 39 years, who completed a mental disorder diagnostic interview and had blood specimens collected after a 12-h fast, as a part of the Third National Health and Nutrition Examination Survey, 1988-1994. The serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were dichotomized according to the recommended levels of the National Cholesterol Education Program. A polytomous logistic regression was employed to control for covariates. RESULTS: Independent of socio-demographic variables, health risks and nutrition status, and a history of medical and psychiatric illness (including depression), a significant association between low HDL-C (< or = 40 mg/dl) and increased prevalence of suicide attempts was observed in women (OR=2.93, 95% CI=1.07-8.00). No significant evidence was found to support an association between cholesterol and suicide ideation in women. Serum cholesterol was unrelated with either suicide ideation or attempts in men. LIMITATION: The inherent limitation of cross-sectional design prevented the authors from investigating causality. CONCLUSIONS: Low HDL-C is significantly associated with suicide attempts in women. Further studies are necessary to explore the clinical application of serum cholesterol as an indicator for suicide attempts among high risk population.

Adolescent↗
PubMed2005

Omission of serial arterial blood sampling in neuroreceptor imaging with independent component analysis.

We have previously proposed a statistical method for extracting a plasma time-activity curve (pTAC) from dynamic PET images, named EPICA, for kinetic analysis of cerebral glucose metabolism. We assumed that the dynamic PET images consist of a blood-related component and a tissue-related component which are spatially independent in a statistical sense. The aim of this study is to investigate the utility of EPICA in imaging total distribution volume (DVt) and binding potential (BP) with Logan plots in a neuroreceptor mapping study. We applied EPICA to dynamic [(11)C]MPDX PET images in 25 subjects, including healthy subjects and patients with brain diseases, and validated the estimated pTACs. [11C]MPDX is a newly developed radiopharmaceutical for mapping cerebral adenosine A1 receptors. EPICA successfully extracted pTAC for all 25 subjects. Parametric images of DVts were estimated by applying Logan plots with the EPICA-estimated pTAC and then used to define a reference region. The BPs estimated using EPICA were evaluated in 18 subjects by ROI-based comparison with those obtained using the nonlinear least squares method (NLSM). The calculated BPs were identical to the estimates using NLSM in each subject. We conclude that EPICA is a promising technique that generates parametric images of DVt and BP in neuroreceptor mapping without requiring arterial blood sampling.

Algorithms↗
PubMed2005

Prediagnostic plasma vitamin C levels and the subsequent risk of prostate cancer.

OBJECTIVE: Antioxidants, such as vitamin C, are hypothesized to prevent prostate carcinogenesis by protecting the DNA from oxidative damage. We assessed whether higher prediagnostic plasma concentrations of vitamin C were associated with a lower risk of prostate cancer in a well-nourished cohort of men. METHODS: Plasma concentrations of ascorbic acid (vitamin C) were previously determined in blood specimens collected between 1984 and 1990 in men participating in the Baltimore Longitudinal Study of Aging. Total plasma ascorbic acid (L-ascorbic acid plus dehydro-L-ascorbic acid) levels were measured by using a modification of the 2,4-dinitrophenylhydrazine method. Among the 498 male participants with measured plasma vitamin C levels, 62 men were subsequently diagnosed with prostate cancer during their lifetime. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for prostate cancer. RESULTS: The median plasma concentration of vitamin C for the cohort was 1.17 mg/dL, which is in the normal to high range for older men. The age-adjusted relative risk of prostate cancer for the highest quartile (median = 1.47 mg/dL, range = 1.36-2.58) compared with the lowest quartile (median = 0.83 mg/dL, range = 0.15-0.98) of plasma vitamin C concentration was 1.31 (95% confidence interval 0.63 to 2.70, P for trend = 0.29). Adjustment for cigarette smoking status, body mass index, or plasma cholesterol concentration did not attenuate the results. CONCLUSIONS: This small but prospective study suggests that higher plasma vitamin C concentrations within the normal physiologic range are not associated with a lower risk of prostate cancer in well-nourished men.

Aging↗
PubMed2006

Elevated levels of serum interleukin-6 are associated with low grade cellular rejection in patients with heart transplantation.

UNLABELLED: Endomyocardial biopsy is the gold-standard procedure to diagnose acute cellular rejection after heart transplantation. This study assessed whether the blood levels of cytokines involved in inflammation and immune activation are useful to detect the presence of acute cellular rejection. METHODS: Blood specimens collected before 275 endomyocardial biopsies in 66 patients were assayed for levels of TNFalpha, IL6, IL1beta, and IL2 receptor. The biopsies were grouped according to the presence (n = 41) or absence (n = 234) of acute cellular rejection grade > or = 3A of the International Society for Heart and Lung Transplantation. We compared the levels of cytokines in the two groups. RESULTS: Circulating IL6 levels were significantly higher when there was a low grade (0-2) cellular rejection in the biopsy versus the group of biopsies grade > or = 3A (19.8 +/- 27 versus 12.9 +/- 10 pg/mL; P = .001). An IL6 level higher than 30 pg/mL showed a negative predictive value of 95% for the presence of acute rejection grade > or = 3A. CONCLUSION: In heart transplant patients, high levels of serum IL6 were associated with low grade cellular rejection. Determination of IL6 levels may be useful to reduce the number of endomyocardial biopsies during follow-up in these patients.

Adult↗