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Background: Stressed, damaged or very aged skin is predominantly characterized by a malfunctioning skin barrier. Underlying skin barrier malfunction is a reduced or defective calcium gradient in the epidermis. Consequently, replenishing the compromised skin's calcium stores with topical calcium could be a potential therapeutic approach., Methods: We investigated the effect of our novel Ca 2+ double cone vector system on improving the differentiation and barrier function of reconstructed human epidermis (RHE), cultured at low basal calcium (0.3 mM) to represent very aged skin. Furthermore, in a randomized placebo-controlled clinical study the skin barrier of 20 healthy volunteers was challenged with 2% sodium lauryl sulphate (SLS) for 24 h under occlusion, following and/or prior to treatment with a gel containing 2% of our calcium vector system., Results: Culture in reduced basal calcium conditions (0.3 mM) strongly impeded the formation of a dense stratified epidermis. The apical treatment with 1.1 mM CaCl 2 was not able to restore a functional differentiation. Treatment with 0.1% of the Ca 2+ delivery system rescued the differentiation process and resulted in a normal stratified epidermis. Clinically, application of the Ca 2+ vector system prior to and following SLS stress prevented increases in skin irritation and transepidermal water loss (TEWL) compared to placebo controls. Importantly, the treatment also significantly accelerated the recovery time following SLS stress., Conclusion: With our novel Ca 2+ vector system, we highlight the delivery of bioavailable Ca 2+ ions into the skin as a new and successful approach to treat a damaged barrier present in stressed, aged or atopic skin., (© 2023 Mibelle AG. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Nutlin-3a is a reversible inhibitor of the p53/MDM2 interaction. We have synthesized the derivative Nutlin-3a-aa bearing an additional exocyclic methylene group in the piperazinone moiety. Nutlin-3a-aa is more active than Nutlin-3a against purified wild-type MDM2, and is more effective at increasing p53 levels and releasing transcription of p53 target genes from MDM2-induced repression. X-ray analysis of wild-type MDM2-bound Nutlin-3a-aa indicated that the orientation of its modified piperazinone ring was altered in comparison to the piperazinone ring of MDM2-bound Nutlin-3a, with the exocyclic methylene group of Nutlin-3a-aa pointing away from the protein surface. Our data point to the introduction of exocyclic methylene groups as a useful approach by which to tailor the conformation of bioactive molecules for improved biological activity., (© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.)

Objective: The purpose of this study was to develop and verify a quantifiable symmetry score for infantile postural and movement asymmetries., Methods: Three studies were conducted. For reliability, 6 test items examining postural and movement asymmetries, which came under consideration, were investigated in 24 infants with postural abnormality (range: 14-24 weeks). The inter-rater reliability was chosen as the primary endpoint. Furthermore, intrarater reliability and test-retest reliability were determined. Analysis and weighting of the items were performed by calculating the intraclass correlation coefficient. The validity was reviewed by expert opinion and by using a study with 26 infants (range: 12-28 weeks) of a cross-section population. The pilot study involved 38 infants, aged 14 to 24 weeks, who were examined using video. Their autonomic symptoms were recorded, and subsequently, they were treated once by means of manual medicine. The parents were instructed to a daily home program that focused on "tummy time.", Results: The reliability tests led to a 4-item symmetry score with a point value between 4 points (very symmetrical) and 17 points (very asymmetrical). The chosen items achieved an intraclass correlation coefficient >0.8 and Cohen's κ >0.6, respectively. The experts' opinions matched mainly to a majority agreement (>50%). Furthermore, a comparison between the outcome of clinical testing and the symmetry score applied to 26 children without diagnosed abnormalities displayed an agreement of 84.6%. The pilot study showed a good reduction of the postural and movement abnormalities because 63% of the manual treated children were assessed as being symmetric afterward., Conclusion: The reliable and valid 4-item symmetry score served for the diagnosis, evaluation, and follow-up of infants aged 3 to 6 months with infantile postural and movement asymmetries. The results of a pilot study showed the positive effect of a single manual medical treatment session along with a home program focusing on "tummy time."

Case study description and analysis of a complex craniovertebral dysplasia in an 8-year-old male patient, in which conventional cervical spine radiographs demonstrated a regularly differentiated occipital base, as well as the presence of two lateral masses of the proatlas vertebra and two lateral masses of the atlas vertebra. Further assessment included computed tomography of the occipital base and the upper cervical spine as well as three-dimensional reconstruction. Malsegmentation of the fourth occipital vertebra can result in various anomalies that are known as 'manifestation of the proatlas'. The occurrence of a persistent proatlas with additional segmentation of the craniovertebral junction represents an extremely rare dysplasia. To our knowledge, it is the second report concerning the persistence of a complete human proatlas vertebra. We consider the biomechanical and embryological particularities of this complex dysplasia to represent sufficient basis for future differentiation from other malformations of the fourth occipital vertebra. Comprehensive literature review and discussion about the entity will be provided.

Background Aims: Wide acceptance of the colony-forming unit (CFU) assay as a reliable potency test for stem cell products is hindered by poor inter-laboratory reproducibility. The goal of this study was to ascertain current laboratory practices for performing the CFU assay with an eye towards identifying practices that could be standardized to improve overall reproducibility., Methods: A survey to evaluate current laboratory practices for performing CFU assays was designed and internationally distributed., Results: There were 105 respondents to the survey, of whom 68% performed CFU assays. Most survey recipients specified that an automated rather than a manual cell count was performed on pre-diluted aliquots of stem cell products. Viability testing methods employed various stains, and when multiple sites used the same viability stain, the methods differed. Cell phenotype used to prepare working cell suspensions for inoculating the CFU assay differed among sites. Most respondents scored CFU assays at 14-16 days of incubation, but culture plates were read with various microscopes. Of 57 respondents, 42% had not performed a validation study or established assay linearity. Only 63% of laboratories had criteria for determining if a plate was overgrown with colonies., Conclusions: Survey results revealed inconsistent inter-laboratory practices for performing the CFU assay. The relatively low number of centers with validated CFU assays raises concerns about assay accuracy and emphasizes a need to establish central standards. The survey results shed light on numerous steps of the methodology that could be targeted for standardization across laboratories., (Copyright © 2013 International Society for Cellular Therapy. All rights reserved.)

A two-step, automated, high-throughput RNAi silencing screen was used to identify host cell factors required during vaccinia virus infection. Validation and analysis of clustered hits revealed previously unknown processes during virus entry, including a mechanism for genome uncoating. Viral core proteins were found to be already ubiquitinated during virus assembly. After entering the cytosol of an uninfected cell, the viral DNA was released from the core through the activity of the cell's proteasomes. Next, a Cullin3-based ubiquitin ligase mediated a further round of ubiquitination and proteasome action. This was needed in order to initiate viral DNA replication. The results accentuate the value of large-scale RNAi screens in providing directions for detailed cell biological investigation of complex pathways. The list of cell functions required during poxvirus infection will, moreover, provide a resource for future virus-host cell interaction studies and for the discovery of antivirals., (Copyright © 2012 The Authors. Published by Elsevier Inc. All rights reserved.)

Isogenic cells in culture show strong variability, which arises from dynamic adaptations to the microenvironment of individual cells. Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image-based RNAi screens. We developed a comprehensive computational approach that employs Bayesian and multivariate methods at the single-cell level. We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome-wide screens, analysing 17 different mammalian virus infections and four related cell physiological processes. Analysing cell-based screens at this depth reveals widespread RNAi-induced changes in the population context of individual cells leading to indirect RNAi effects, as well as perturbations of cell-to-cell variability regulators. We find that accounting for indirect effects improves the consistency between siRNAs targeted against the same gene, and between replicate RNAi screens performed in different cell lines, in different labs, and with different siRNA libraries. In an era where large-scale RNAi screens are increasingly performed to reach a systems-level understanding of cellular processes, we show that this is often improved by analyses that account for and incorporate the single-cell microenvironment.

Frequent blood donors become iron deficient. HFE mutations are present in over 30% of donors. A 24-month study of 888 first time/reactivated donors and 1537 frequent donors measured haemoglobin and iron status to assess how HFE mutations impact the development of iron deficiency erythropoiesis. Donors with two HFE mutations had increased baseline haemoglobin and iron stores as did those with one mutation, albeit to a lesser extent. Over multiple donations haemoglobin and iron status of donors with HFE mutations paralleled those lacking mutations. The prevalence of HFE mutations was not increased in higher intensity donors. Thus, in general, HFE mutations do not temper donation-induced changes in haemoglobin and iron status. However, in Black donors there was an increase of H63D carriers at baseline, from 3·7% in first time/reactivated donors to 15·8% in frequent donors, suggesting that the relative effects of HFE mutations on iron absorption may vary between racial/ethnic groups. In secondary analyses, venous haemoglobin decreased more slowly in donors with ferritin ≥12μg/l; and haemoglobin recovery time was shorter in donors with reticulocyte haemoglobin (CHr) ≥32·6pg, indicating that these biochemical measures are better indicators of a donor's response to phlebotomy than their HFE mutation status., (© 2011 Blackwell Publishing Ltd.)

The pathogen Salmonella Typhimurium is a common cause of diarrhea and invades the gut tissue by injecting a cocktail of virulence factors into epithelial cells, triggering actin rearrangements, membrane ruffling and pathogen entry. One of these factors is SopE, a G-nucleotide exchange factor for the host cellular Rho GTPases Rac1 and Cdc42. How SopE mediates cellular invasion is incompletely understood. Using genome-scale RNAi screening we identified 72 known and novel host cell proteins affecting SopE-mediated entry. Follow-up assays assigned these 'hits' to particular steps of the invasion process; i.e., binding, effector injection, membrane ruffling, membrane closure and maturation of the Salmonella-containing vacuole. Depletion of the COPI complex revealed a unique effect on virulence factor injection and membrane ruffling. Both effects are attributable to mislocalization of cholesterol, sphingolipids, Rac1 and Cdc42 away from the plasma membrane into a large intracellular compartment. Equivalent results were obtained with the vesicular stomatitis virus. Therefore, COPI-facilitated maintenance of lipids may represent a novel, unifying mechanism essential for a wide range of pathogens, offering opportunities for designing new drugs., (© 2011 EMBO and Macmillan Publishers Limited)

Unlabelled: CellClassifier is a tool for classifying single-cell phenotypes in microscope images. It includes several unique and user-friendly features for classification using multiclass support vector machines, Availability: Source code, user manual and SaveObjectSegmentation CellProfiler module available for download at www.cellclassifier.ethz.ch under the GPL license (implemented in Matlab).

Single-cell heterogeneity in cell populations arises from a combination of intrinsic and extrinsic factors. This heterogeneity has been measured for gene transcription, phosphorylation, cell morphology and drug perturbations, and used to explain various aspects of cellular physiology. In all cases, however, the causes of heterogeneity were not studied. Here we analyse, for the first time, the heterogeneous patterns of related cellular activities, namely virus infection, endocytosis and membrane lipid composition in adherent human cells. We reveal correlations with specific cellular states that are defined by the population context of a cell, and we derive probabilistic models that can explain and predict most cellular heterogeneity of these activities, solely on the basis of each cell's population context. We find that accounting for population-determined heterogeneity is essential for interpreting differences between the activity levels of cell populations. Finally, we reveal that synergy between two molecular components, focal adhesion kinase and the sphingolipid GM1, enhances the population-determined pattern of simian virus 40 (SV40) infection. Our findings provide an explanation for the origin of heterogeneity patterns of cellular activities in adherent cell populations.

The use of normal immersion oil, developed for 23 degrees C, at 37 degrees C greatly compromises both axial resolution and signal intensity. We developed and characterized an immersion oil for optimal performance in live-cell imaging at 37 degrees C. We quantify the improvements in resolution and intensity obtained when using the new oil instead of its standard 23 degrees C counterparts.

Mammalian cell biology is witnessing a new era in which cellular processes are explained through dynamic networks of interacting cellular components. In this fast-pacing field, where image-based RNAi screening is taking a central role, there is a strong need to improve ways to capture such interactions in space and time. Cell biologists traditionally depict these events by confining themselves to the level of a single cell, or to many population-averaged cells. Similarly, classical geneticists observe and interpret phenotypes in a single organism to delineate signaling processes, but have also described genetic phenomena in populations of organisms. The analogy in the two approaches inspired us to draw parallels with, and take lessons from concepts in classical genetics.

Background: Understanding the variability in results obtained by multiple laboratories is important because cord blood units are distributed worldwide for transplantation., Study Design and Methods: Four exercises were conducted by multiple laboratories to assess assay variability on nucleated cell (NC), mononuclear cell (MNC) by hematology analyzers [HAs], and CD34+ cell (flow cytometry) measurements. Exercise 1 was an intralaboratory exercise in which the reproducibility of cell measurements was determined. Exercises 2 and 3 involved the shipment of identical processed cord blood samples. In Exercise 2, laboratory-specific methods were utilized. In Exercise 3, two commercial CD34+ cell methods (Stem-Kit and TruCOUNT) were used. In Exercise 4, CD34+ cell levels were determined on repetitive regating of identical list-mode files., Results: Intralaboratory reproducibility was highest for NC measurements and lowest for CD34+ cell measurements. In Exercise 2, all laboratories except one utilized HA with an impedance technology and determined comparable results for NC and MNC levels, whereas the other laboratory utilized a HA with an optical counting method. Substantial variation was observed on measuring CD34+ cells with ranges of 32 to 141, 32 to 66, and 25 to 116 CD34+ cells per microL for the three identical samples. In Exercise 3, on the use of one specific commercial assay, the ranges of CD34+ levels were 214 to 411 and 62 to 178 cells per microL for the two identical samples. Nearly all participating laboratories determined comparable CD34+ levels on the use of identical list-mode files., Conclusion: These studies indicate that substantial variability in CD34+ cell levels were determined with flow cytometry. The variability in NC and MNC levels was minimal with HA methodology.

Objective: Little is known about the association between fetal thrombophilias and severe preeclampsia. The objective of this study was to examine the association between fetal genotype for factor V Leiden, prothrombin, and methylene tetrahydrofolate reductase (MTHFR) mutations and severe preeclampsia., Methods: Patients with severe preeclampsia or HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome admitted to Georgetown University Hospital were retrospectively identified. Controls were patients with uncomplicated, term deliveries. Fetal DNA was extracted from placental specimens and amplified by polymerase chain reaction (PCR) with locus-specific primers. The presence of polymorphisms was determined by enzymatic digestion with specific enzymes, and analyzed by polyacrylamide gels. Statistical analysis used Student t test for continuous variables and Fisher exact test for categorical data., Results: Patients with preeclampsia (n = 27) and controls (n = 17) were similar for maternal age, but, as expected, they were significantly different for gestational age at delivery, birth weight, Apgar scores at 5 minutes, rate of preterm delivery less than 37 weeks, and fetal growth restriction (all P <.05). DNA extraction was successful in 25 of 27 cases from the severe preeclampsia group and 14 of 17 controls. None of the placentas analyzed in the preeclamptic or control group revealed mutations in the factor V Leiden or prothrombin genes. There was no significant difference in the rate of fetuses heterozygous for MTHFR in the preeclampsia versus control group (48% vs 43%, P >.05)., Conclusion: In our study, fetal genotype for specific inherited thrombophilias does not appear to be associated with severe preeclampsia.

Purpose: The frontal axial angle of the occipitoatlantal complex in adults is well known. Clinical radiological investigations of the infantile cervical spine indicate other proportions. Extensive radiological studies concerning the postnatal development of the frontal axial angle are unknown. Knowledge about the special biomechanical relation of the infantile cervical spine is necessary for understanding several high cervical irritation syndromes in newborns., Materials and Methods: To measure the occipitoatlantal angle C0/C1, 1016 AP radiographs of the upper cervical spine were investigated. The radiographs were obtained on female and male patients ranging from 0 - 10 years of age., Results: The frontal axial angle C0/C1 is distinctly flatter in infants (153 degrees in newborns at the age of 0 to 3 months) and only approaches an adult state after the 10 th year of life., Conclusion: The distinctly flatter configuration of the frontal axial angle C0/C1 in newborns could be interpreted as constituting a different morphology for better adaptation to the biomechanical strain of the upper cervical spine during labor. The postnatal development of the frontal axial angle of the occipitoatlantal complex is illustrated.

Intravenous immunoglobulin (IVIG) preparations are a mainstay for a number of disorders that include primary immuno-deficiency, acute inflammatory conditions, hematological disorders, infections, and neuroimmunological disorders. The range of therapeutic activity is attributed to IVIG's myriad action mechanisms. IVIG can interact and bind onto complement factors, which can prevent complement-mediated tissue damage, modulate T-lymphocytes, alter cytokine profiles, and modulate the immune system. These interactions can act alone or in combination to maintain immune balance while preserving homeostasis. A consensus panel was convened in 2000 to evaluate and define new advances in IVIG therapies.

Context: The human T-lymphotropic viruses types 1 and 2 (HTLV-1 and HTLV-2) are highly prevalent among injection drug users in the United States. However, the clinical course of infection has not been well characterized., Objective: To understand HTLV-1-and HTLV-2-associated laboratory abnormalities, which may provide insights into their underlying pathophysiology., Design: Cohort study., Setting: Five US blood centers., Participants: A total of 133 HTLV-1-and 332 HTLV-2-seropositive former blood donors and 717 HTLV-seronegative donors followed up prospectively since 1991., Main Outcome Measures: Selected serum chemistry tests and complete blood cell counts were analyzed at enrollment and approximately 2 years later in participants. Repeated-measures analyses were conducted to evaluate the effect of HTLV infection on laboratory measures., Results: Compared with seronegative subjects, HTLV-1-seropositive subjects had 13% higher creatine kinase (P =.02) and slightly elevated lactate dehydrogenase (P =.03) levels at follow-up. The HTLV-2-seropositive participants had 11% higher absolute lymphocyte counts than seronegative subjects (P =.0001). Infection with HTLV-2 also appeared to be associated with slightly higher hemoglobin levels (P =.03) and hematocrit (P =.03) and with lower albumin levels (P =.01)., Conclusions: These results further our understanding of the biological mechanisms underlying HTLV and suggest that HTLV-associated laboratory changes are unlikely to alter clinical evaluation or counseling of otherwise healthy HTLV-infected subjects.

The final decade of the last century of the second millennium ad has seen dramatic changes in all aspects of science and health care. In transfusion medicine, the blood supply is the safest it has ever been. Newer refinements and innovations are continuously being researched and implemented to achieve and further enhance safety. Advances in blood conservation, pharmacologic manipulation, engineered blood derivatives, and recombinant growth factors can now provide safer and more effective alternatives to blood transfusions for many patients. This overview highlights selective innovations in transfusion medicine and emphasizes some significant advances that have occurred in blood donor screening, blood component collections and therapy, and laboratory testing. Newer technologies are anticipated that will further enhance the safety of blood and transfusions and potentially augment annually the blood supply on a worldwide basis.

Background: To determine whether human T-lymphotropic virus type II (HTLV-II) infection is associated with an increased incidence of bacterial infections, we prospectively observed cohorts of HTLV-I- and HTLV-II-infected and seronegative subjects in 5 US cities., Methods: Of 1340 present and former blood donors examined at enrollment, 1213 (90.5%) were re-examined after approximately 2 years, including 136 HTLV-I- and 337 HTLV-II-seropositive subjects and 740 demographically stratified HTLV-seronegative subjects. All subjects were seronegative for human immunodeficiency virus. Odds ratios (ORs) for incident disease outcomes were adjusted for covariates, including age, sex, race or ethnicity, education, and, if significantly associated with the outcome, blood center, donation type, income, smoking, alcohol intake, and injected drug use., Results: Compared with seronegative status, HTLV-II infection was associated with an increased incidence of bronchitis (OR, 1.81; 95% confidence interval [CI], 1.20-2.75), bladder and/or kidney infection (OR, 1.94; 95% CI, 1.26-2.98), oral herpes infection (OR, 9.54; 95% CI, 3.33-27.32), and a borderline increased incidence of pneumonia (OR, 2.09; 95% CI, 0.92-4.76); HTLV-I infection was associated with an increased incidence of bladder and/or kidney infection (OR, 2.79; 95% CI, 1.63-4.79). One incident case of HTLV-I-positive adult T-cell leukemia was observed (incidence, 348 per 100,000 HTLV-I person-years), and 1 case of HTLV-II-positive tropical spastic paraparesis-HTLV-associated myelopathy was diagnosed (incidence, 140 per 100,000 HTLV-II person-years)., Conclusions: These data support an increased incidence of infectious diseases among otherwise healthy HTLV-II- and HTLV-I-infected subjects. They are also consistent with the lymphoproliferative effects of HTLV-I, and with neuropathic effects of HTLV-I and HTLV-II.

Large lymphocytes with basophilic cytoplasm and cleaved/cerebriform nuclei called flower cells have been described in human T-lymphotrophic virus type I (HTLV-I) seropositive individuals and may be precursors of adult T-cell leukaemia (ATL). A cohort of 546 HTLV-seropositive former blood donors, 32 HTLV-positive sexual partners of these donors and 799 HTLV-seronegative controls has been followed as part of the Retrovirus Epidemiology Donor Study. A novel methodology was developed to systematically review peripheral blood slides from these subjects for HTLV-related lymphocyte abnormalities, using an algorithm based on morphologic features to objectively identify flower cells. The algorithm included: absence of azurophil granules; nuclear chromatin condensation; cell size >1.5 small lymphocytes; nuclear to cytoplasmic ratio >80%; and presence of nuclear folding/lobulation. Peripheral slides from subjects were screened by a medical technologist blinded to HTLV status. 6.8% of HTLV-I subjects (P = 0.0001 versus seronegatives), 0.9% of HTLV-II subjects and 1.1% of seronegatives were confirmed to have cells classified as flower cells by two haematologists using objective criteria, and blinded to serostatus. Despite the higher prevalence of flower cells in HTLV-I positives, no clinical correlations were found. Longitudinal follow-up may yield higher rates of cellular abnormalities as the sequelae of HTLV infection develop.

Reports of laboratory abnormalities associated with HTLV-I and HTLV-II infection are inconsistent. We assessed complete blood counts and selected serum chemistry measures at enrollment in a cohort of 153 HTLV-I-seropositive, 386 HTLV-II-seropositive, and 795 HTLV-seronegative blood donors. Linear and logistic regression were used to adjust for potential confounding variables including age, gender, race/ethnicity, education level, blood center, and injection drug use. Compared with seronegative donors, absolute lymphocyte counts were 6% and 10% higher, on average, in HTLV-I-infected (p = .03) and HTLV-II-infected (p = .0001) donors, respectively. HTLV-I- and HTLV-II-seropositive donors had, on average, 17,630 (p = .003) and 15,160 (p = .0005) more platelets, respectively. HTLV-I-infected donors also had an average of 30 fewer eosinophils/microl (p = .003) and a slightly higher level of lactic dehydrogenase (p = .05). HTLV-II-infected subjects had on average, an 11% decrease in creatine kinase (p = .006), a minor increase in mean corpuscular volume (p = .01), and a slightly lower serum calcium level (p = .0005). These results indicate that both HTLV-I and HTLV-II may raise levels of lymphocytes and platelets by unknown mechanisms. Lower eosinophil counts may be related to the increased susceptibility of HTLV-I-infected subjects to parasitic diseases.

Objective: To compare the transfusion practices between two neonatal intensive care units (NICUs) to assess the impact of local practice styles on the timing, number, and total volume of packed red cell transfusions in very low birth weight infants. To derive multivariate models to describe practice and to identify potential areas for improvement in the future., Methodology: We reviewed phlebotomy losses and transfusion rates between two NICUs (A and B) for 270 consecutive admissions of birth weight < 1500 g. We stratified for birth weight and for illness severity by the Score for Neonatal Acute Physiology (SNAP). Measures of short-term outcome were compared. We derived multivariate models to describe and compare the practices in the two NICUs., Results: Patients in NICU A had smaller phlebotomy losses than those in NICU B. A lower percentage of the patients in NICU A (65% vs 87%) received transfusions, but they tended to receive a greater total volume per kg per patient (67 mL/kg vs 54.8 mL/kg). Transfusion timing differed between the NICUs; in NICU A only approximately one-half of their transfusions occurred in the first 2 weeks, whereas in NICU B almost 70% of the transfusions were given in this time period. Multivariate models showed that phlebotomy losses were significantly related to lower gestational age (GA) and higher SNAP. Hospitalization in NICU B resulted in 10.7 cc of additional losses relative to NICU A for a comparable GA and illness severity score. The volume of blood transfused per kilogram of body weight was a function of GA, SNAP, and hospital. Care practices in NICU A added an additional 19 cc of transfused volume in the first 14 days of life, and an additional 26 cc thereafter when adjusted for GA and SNAP. These differences in phlebotomy and transfusion were not associated with differences in the days of oxygen therapy or mechanical ventilation, the oxygen requirement at 28 days, the incidence of chronic lung disease, or the rate of growth by day 28., Conclusions: We identified significant differences in phlebotomy and transfusion practices between two NICUs. We found no differences in short-term outcome, suggesting that the additional use of blood in one of the NICUs was discretionary rather than necessary. Our multivariate models can be used to characterize and quantify transfusion and phlebotomy practices. By predicting which patients are likely to require multiple transfusions, clinicians can target patients for erythropoietin therapy and identify those patients for whom donor exposure can be reduced by a unit of blood for multiple use. The models may help in monitoring changes in practice as they occur.

Disease associations of human T lymphotropic virus types I and II (HTLV-I and -II) infection were studied in 154 HTLV-I-infected, 387 HTLV-II-infected, and 799 uninfected blood donors. Adjusted odds ratios (ORs) and 99% confidence intervals (CIs) were derived from logistic regression models controlling for demographics and relevant confounders. All subjects were human immunodeficiency virus type 1-seronegative. HTLV-II was significantly associated with a history of pneumonia (OR, 2.6; 99% CI, 1.2-5.3), minor fungal infection (OR, 2.9; 99% CI, 1.2-7.1), and bladder or kidney infection (OR, 1.6; 99% CI, 1.0-2.5) within the past 5 years and with a lifetime history of tuberculosis (OR, 3.9; 99% CI, 1.3-11.6) and arthritis (OR, 1.8; 99% CI, 1.2-2.9). Lymphadenopathy (> or =1 cm) was associated with both HTLV-I (OR, 6.6; 99% CI, 2.2-19.2) and HTLV-II (OR, 2.8; 99% CI, 1.1-7.1) infection, although no case of adult T cell leukemia/lymphoma was diagnosed. Urinary urgency and gait disturbance were associated with both viruses. This new finding of increased prevalence of a variety of infections in HTLV-II-positive donors suggests immunologic impairment.