Retrospective analysis of forward and reverse ABO typing discrepancies among patients and blood donors in a tertiary care hospital.

OBJECTIVE: The aim of our study was to determine the incidence and causes of ABO typing discrepancies among patients and blood donors at our centre. BACKGROUND: An accurate interpretation of the ABO blood group of an individual is of utmost importance to ensure patient safety and good transfusion practices. METHODS: A retrospective observational study was carried out in the Department of Transfusion Medicine in our hospital from March 2013 to December 2015. Records of all patient and blood donor samples were retrieved and analysed for ABO typing discrepancies. RESULTS: In total, 135 853 patient and 62 080 donor samples were analysed for ABO typing discrepancies. The incidence among patients and blood donors was found to be 0·1% (138/135853) and 0·02% (14/62080), respectively. The mean age for patients and blood donors was 48·4 and 29·2 years, respectively. The most common cause of ABO typing discrepancies was due to cold autoantibodies among the patients (50·7%) and blood donors (57%) causing discrepant results in reverse typing. The various other causes of reverse typing discrepancies among patients were weak/missing antibody (25·4%), cold-reacting alloantibody (4·3%), warm autoantibody (2·2%), anti-A1 antibody (2·2%), Bombay phenotype (1·5%), transplantation (0·7%) and rouleaux (0·7%), whereas in blood donors, the causes were cold-reacting antibody (7%) and weak antibody (7%). The major cause of forward typing discrepancies among patients (12·3%) and blood donors (29%) was ABO subgroups. CONCLUSION: The resolution of ABO typing discrepancy is essential to minimise the chance of transfusion of ABO-incompatible blood.

Induction of robust de novo centrosome amplification, high-grade spindle multipolarity and metaphase catastrophe: a novel chemotherapeutic approach.

Centrosome amplification (CA) and resultant chromosomal instability have long been associated with tumorigenesis. However, exacerbation of CA and relentless centrosome declustering engender robust spindle multipolarity (SM) during mitosis and may induce cell death. Recently, we demonstrated that a noscapinoid member, reduced bromonoscapine, (S)-3-(R)-9-bromo-5-(4,5-dimethoxy-1,3-dihydroisobenzofuran-1-yl)-4-methoxy-6-methyl-5,6,7,8-tetrahydro-[1,3]dioxolo-[4,5-g]isoquinoline (Red-Br-nos), induces reactive oxygen species (ROS)-mediated autophagy and caspase-independent death in prostate cancer PC-3 cells. Herein, we show that Red-Br-nos induces ROS-dependent DNA damage that resulted in high-grade CA and SM in PC-3 cells. Unlike doxorubicin, which causes double-stranded DNA breaks and chronic G2 arrest accompanied by 'templated' CA, Red-Br-nos-mediated DNA damage elicits de novo CA during a transient S/G2 stall, followed by checkpoint abrogation and mitotic entry to form aberrant mitotic figures with supernumerary spindle poles. Attenuation of multipolar phenotype in the presence of tiron, a ROS inhibitor, indicated that ROS-mediated DNA damage was partly responsible for driving CA and SM. Although a few cells (∼5%) yielded to aberrant cytokinesis following an 'anaphase catastrophe', most mitotically arrested cells (∼70%) succumbed to 'metaphase catastrophe,' which was caspase-independent. This report is the first documentation of rapid de novo centrosome formation in the presence of parent centrosome by a noscapinoid family member, which triggers death-inducing SM via a unique mechanism that distinguishes it from other ROS-inducers, conventional DNA-damaging agents, as well as other microtubule-binding drugs.

A novel microtubule-modulating noscapinoid triggers apoptosis by inducing spindle multipolarity via centrosome amplification and declustering.

We have previously shown that a non-toxic noscapinoid, EM011 binds tubulin without altering its monomer/polymer ratio. EM011 is more active than the parent molecule, noscapine, in inducing G2/M arrest, inhibiting cellular proliferation and tumor growth in various human xenograft models. However, the mechanisms of mitotic-block and subsequent cell death have remained elusive. Here, we show that EM011-induced attenuation of microtubule dynamics was associated with impaired association of microtubule plus-end tracking proteins, such as EB1 and CLIP-170. EM011 treatment then led to the formation of multipolar spindles containing 'real' centrioles indicating drug-induced centrosome amplification and persistent centrosome declustering. Centrosome amplification was accompanied by an upregulation of Aurora A and Plk4 protein levels, as well as a surge in the kinase activity of Aurora A, suggesting a deregulation of the centrosome duplication cycle. Cell-cycle phase-specific experiments showed that the 'cytotoxicity-window' of the drug encompasses the late S-G2 period. Drug-treatment, excluding S-phase, not only resulted in lower sub-G1 population but also attenuated centrosome amplification and spindle multipolarity, suggesting that drug-induced centrosome amplification is essential for maximal cell death. Subsequent to a robust mitotic arrest, EM011-treated cells displayed diverse cellular fates suggesting a high degree of intraline variation. Some 'apoptosis-evasive' cells underwent aberrant cytokinesis to generate rampant aneuploidy that perhaps contributed to drug-induced cell death. These data indicate that spindle multipolarity induction by means of centrosome amplification has an exciting chemotherapeutic potential that merits further investigation.

Passive transfer of hepatitis antibodies during intravenous administration of immune globulin.

We studied the effect of intravenous immune globulin (IVIG) infusion on the levels of hepatitis B and C antibodies in 10 premature babies. All four tested lots of a commercially purchased IVIG preparation were found to contain substantial amounts of hepatitis B core and hepatitis C antibodies. Our results show that passive transfer of hepatitis B and C virus antibodies occurred after IVIG infusion, and that the levels were dependent on the quantity of IVIG given. When assessing neonates for hepatitis, the factor of receipt of blood products, including IVIG, needs to be considered to interpret laboratory results.

Diphallus and associated anomalies with balanced autosomal chromosomal translocation.

We report a sporadic case of complete diphallus with multiple other anomalies in a premature newborn. Chromosomal analysis at the 500 band level showed an apparently balanced reciprocal translocation 46,XY, t(1;14)(p36.3;q24.3). The mother has a normal karyotype, but the father was not available for chromosomal analysis. The significance of this balanced chromosomal rearrangement and the possibility that the chromosomal breakpoints contribute to deregulation of mesodermal development is discussed.

Population pharmacokinetics of ceftizoxime in premature newborns.

The population pharmacokinetic parameters of ceftizoxime were determined in 50 premature newborns less than 1 week of age (birth weight = 1.8 +/- 0.6 kg) with a clinical diagnosis of suspected sepsis. Each infant received ceftizoxime 25 mg/kg every 12 h intravenously over 30 min for a total of 6 doses. Serum concentrations of ceftizoxime were assayed by HPLC at 0.5, 1, 2.5 and 11.5 h or at 0.5, 1.5, 4.5 and 11.5 h after the first and the sixth dose. A total of 184 serum concentrations following the first dose and 160 following the sixth dose were fit separately and then collectively to a one-compartment model using NONMEM. The separately estimated parameters were not significantly different between the first and the sixth dose. The final parameter estimates were 27.1 ml/h/kg, 333 ml/kg and 8.5 h for clearance, volume of distribution and half-life, respectively. Other factors including gestational and postnatal age were not associated with alterations in ceftizoxime clearance. That the large variability in clearance was decreased from a coefficient of variation of 80 to 50% warrants dosing premature infants on the basis of body weight. The results of this study suggest that 25 mg/kg ceftizoxime every 12 h appears to be an appropriate dosing regimen for premature neonates.

Developmental follow-up of very low birthweight premature infants with low free thyroxine.

If a low level of free thyroxine (T4) is predictive of the true hypothyroidism in sick premature infants, long-term developmental follow-up of these infants should reveal a direct correlation between the free thyroxine level early in life and developmental disability in later years. Half of the 16 infants who were followed had normal free T4 (0.8 ng/dl or higher) and the remaining 8 infants had a low free T4 (0.38 +/- 0.15 ng/dl) during the first 2 weeks of life. Infants with low free T4 were followed sequentially during their stay in the neonatal intensive care unit and all eight showed free T4 levels more than 0.8 ng/dl by 36 to 44 weeks postconceptional age without any thyroid replacement. At follow-up, all 16 infants were functioning within normal range by Stanford-Binet testing at mean age of 4.6 years. There was no significant difference between the two groups in their motor development, hearing, language, or physical growth. Despite the small sample size, it appears there is no correlation between the free T4 levels during the first 2 weeks of life in infants 33 weeks' or less gestation and their developmental outcome at mean age of 4.6 years.

Effect of fluids on life span of peripheral arterial lines.

This study examines the effect of two different fluids to maintain peripheral arterial line patency at 1 to 2 ml/hr in a randomized controlled trial. Sixty sick newborn infants requiring ventilatory support and frequent blood gas monitoring were randomly assigned to receive either heparinized normal saline (HNS) or heparinized 5% dextrose water (HD5W) to maintain peripheral arterial line patency. One unit of heparin was added to each mililiter of both solutions. The duration of functional arterial lines, sodium balance, and number of peripheral punctures for blood glucose monitoring were compared using Student's t test for independent samples. HNS peripheral arterial catheters functioned significantly longer than HD5W without increased risk of hypernatremia. We conclude that HNS in arterial catheters is safe, lasts longer, and saves the infant (1500 gm or more) from the unnecessary stress of multiple peripheral punctures for blood glucose measurements, which can be obtained from the arterial catheter if glucose is not part of the infusate.

Intermamillary indices in premature infants.

The internipple distance and its relationship to gestational age has not been studied in infants born in the United States. One hundred and thirty-three newborns between 25 and 40 weeks gestation showed progressive increase in the internipple distance with increasing gestational age. The internipple index stays constant during various gestational ages. The internipple index greater than 28% (greater than 2 SD) at any gestational age or during immediate postnatal age should be flagged to look into widely spaced nipples. Extrauterine growth of internipple distance is similar to that of intrauterine growth.

Amino acid mixture designed to maintain normal plasma amino acid patterns in infants and children requiring parenteral nutrition.

A mixture of amino acids designed to maintain normal plasma amino acid concentrations of infants and children requiring parenteral nutrition was evaluated in 40 infants and children receiving only parenteral nutrients (2.39 +/- 0.26 g/kg/d of amino acids and 110.3 +/- 10.4 kcal/kg/d) for five to 21 days. The children ranged in weight from 2.0 to 12.6 kg (median weight, 3.83 kg; fifth to 95th percentile, 2.06 to 11.1 kg) and in age from 1 week to 43.6 months (median age, 2.7 months; fifth to 95th percentile, 0.2 to 25.3 months). Mean weight gain was 11.0 +/- 5.0 g/kg/d; mean nitrogen balance was 242 +/- 70 mg/kg/d. Plasma concentrations of all amino acids except tyrosine were within the normal range (ie, within the 95% confidence limits of the two-hour postprandial plasma concentrations observed in 30-day-old, healthy, normally growing, breast-fed, term infants) throughout the period of study. Mean prestudy and poststudy serum total protein, albumin, and transthyretin (prealbumin) concentrations were not significantly different. However, plasma transthyretin concentration increased in all children with low prestudy concentrations. Mean poststudy serum total bilirubin concentration of the total population was not different from the mean prestudy concentration. This was true also for the 31 children who received the parenteral amino acid mixture for more than ten days. In contrast to the expected 30% to 50% incidence of cholestasis, only one of these 31 experienced an unexplained increase in serum total bilirubin concentration during study, suggesting that normalizing plasma amino acid concentrations and/or providing taurine during parenteral nutrition may decrease the incidence of cholestasis associated with this therapy.

Comparison of the effect of asphyxia, hypoxia, and acidosis on intestinal blood flow and O2 uptake in newborn piglets.

The aim of our study was to compare the effects of asphyxia and the two components of asphyxia, i.e. hypoxia and acidosis, on intestinal blood flow and oxygen consumption in anesthetized newborn piglets less than 3 days old. The first series of experiments, consisting of four groups of piglets, showed that blood flow to the proximal and distal small intestine and colon (as determined by the microsphere technique) significantly decreased after piglets were subjected to a sustained hypoxic hypoxemia (PaO2 50% of control) or asphyxia (acidosis plus hypoxia) for 90 min. A sustained acidosis (arterial pH = 7.0-7.15 for 90 min), however, decreased blood flow only to the proximal small intestine, and sham operation did not significantly alter any intestinal blood flow. All animals subjected to asphyxia and two of five of the animals subjected to hypoxia alone in this series, produced gross and microscopic intestinal lesions similar to those seen in human newborn with necrotizing enterocolitis. Acidosis alone, however, did not produce any pathologic lesions. The second series of experiments showed that the 90-min hypoxic hypoxemia decreased blood flow to both the mucosa and muscularis layers of the small intestine. The third series of experiments, consisting of four groups of piglets, determined the effects of 60-min acidosis, hypoxic hypoxemia, asphyxia, or sham operation on venous outflow and oxygen consumption of the isolated in situ terminal ileum. Acidosis or sham operation altered neither ileal blood flow nor oxygen consumption. Hypoxia or asphyxia, however, decreased ileal oxygen consumption without significantly decreasing blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Gentamicin dosing in the newborn. Use of a one-compartment open pharmacokinetic model to individualize dosing.

Gentamicin 2.5 mg/kg was given to 60 term and preterm neonates. Serum gentamicin concentrations were determined at 1, 7 and 11 h postinfusion. Linear regression analysis was used to determine half-life and volume of distribution. From these data a new dosing regimen and a predicted steady-state peak and trough gentamicin concentration were determined for each neonate. The predicted peak and trough were compared to a measured peak or trough drawn at least 48 h later. Criteria for successful peaks were met in 93% of the patients, while criteria for successful troughs were met in 83%. Individualized gentamicin dosing in the newborn based on a one-compartment open pharmacokinetic model is a useful clinical tool in predicting peak and trough gentamicin concentrations.

Monitoring critically ill newborn infants with digital capillary blood samples: an alternative.

Capillary blood samples obtained from a warmed distal phalanx of the right hand were compared with either temporal or right radial arterial blood samples for PO2, PCO2, and pH in 33 critically ill newborn infants. The blood pressure and skin temperatures of each infant and the ambient oxygen concentration were recorded at the time the blood was sampled. Sixty-eight paired PO2 analyses yielded a regression line close to the line of identity. The mean difference between digital capillary and arterial PO2 was 11.3 +/- 1.4 mm Hg (r = 0.92). The results were similar for the paired PCO2 analyses (r = 0.84) and for the paired pH analyses (r = 0.94). The correlation between arterial PO2 and digital capillary PO2 deteriorated when the systolic blood pressure of the patient was below 35 mm Hg. There was no correlation between skin temperature and capillary-arterial PO2 differences. The frequency of retrolental fibroplasia leading to blindness was not different from that in nurseries that sample umbilical arterial blood routinely.