bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperlactatemia in Human Immunodeficiency Virus–Uninfected Infants Who Are Exposed to Antiretrovirals
Authors: Noguera Antoni , Fortuny Claudia , Muñoz-Almagro Carmen , Sanchez Emilia , Vilaseca M. Antonia , Artuch Rafael , Pou Jordi , Jimenez Rafael 
Published: October 2004

Objective. Exposure to nucleoside analogues in fetal or early life has been associated with rare clinically significant mitochondrial toxic effects, mainly neurologic symptoms. Lactate (LA) measurements have been used to monitor nucleoside-related mitochondrial toxicity. Our aim was to determine the prevalence, clinical evolution, and risk factors for hyperlactatemia in our cohort of human immunodeficiency virus (HIV)-uninfected children who were exposed to antiretrovirals.
Methods. We conducted a prospective observational study of 127 HIV-uninfected infants who were born to HIV-infected women. Clinical symptoms suggesting mitochondrial dysfunction were analyzed in routine follow-up, and LA and alanine plasma levels were obtained at 6 weeks, 3 months, 6 months, and 12 months in all patients. Elevated alanine levels, together with hyperlactatemia, suggest chronic mitochondrial injury.
Results. Most (85%) women received highly active antiretroviral therapy (HAART) during pregnancy (mean duration: 31 weeks) and zidovudine during labor (93%). Most (96%) children received zidovudine alone. Hyperlactatemia with hyperalaninemia was detected in 63 children in at least 1 of the measurements. Mean LA levels were significantly higher in children who were exposed to nucleoside analogue reverse transcriptase inhibitors than in control subjects (2.88 vs 1.61 at 6 weeks, 2.78 vs 1.49 at 3 months, 1.89 vs 1.39 at 6 months, and 1.71 vs 1.24 at 12 months; peak levels: 8.06, 10.1, 7.28, and 4.48 mmol/L, respectively). In 44 patients, LA levels progressed spontaneously to normality within the first year of life. Three girls presented a slight and self-limited delay in psychomotor development, with LA peak levels of 7.3, 4.0, and 4.6 mmol/L. Only the gestational use of didanosine was associated with a higher risk of hyperlactatemia.
Conclusions. In our series, almost half of the children (63 of 127) who were exposed to nucleoside analogues developed benign and self-limited hyperlactatemia. When symptomatic, nucleoside analogue–induced toxicity affected neurologic development.
Hand Hygiene Practices in a Neonatal Intensive Care Unit: A Multimodal Intervention and Impact on Nosocomial Infection
Authors: Lam Barbara C.C. , Lee Josephine , Lau Y.L. 
Published: October 2004

Objective. Health care–associated infections persist as a major problem in most neonatal intensive care units. Hand hygiene has been singled out as the most important measure in preventing hospital-acquired infection. However, hand hygiene compliance among health care workers (HCWs) remains low. The objective of this study was to assess the frequency and nature of patient contacts in neonatal intensive care units and observe the compliance and technique of hand hygiene among HCWs before and after the implementation of a multimodal intervention program.
Methods. The nature and frequency of patient contacts, the hand hygiene compliance, and hand-washing techniques of HCWs were observed unobtrusively to reflect the baseline compliance and to investigate factors for noncompliance. The intervention consisted of problem-based and task-orientated hand hygiene education, enhancement of minimal handling protocol and clustering of nursing care, liberal provision of alcohol-based hand antiseptic, improvement in hand hygiene facilities, ongoing regular hand hygiene audit, and implementation of health care–associated infection surveillance. The observational study was repeated 6 months after the completion of the intervention program, which extended over 1-year period.
Results. Overall hand hygiene compliance increased from 40% to 53% before patient contact and 39% to 59% after patient contact. More marked improvement was observed for high-risk procedures (35%–60%). The average number of patient contacts also decreased from 2.8 to 1.8 per patient per hour. There was improvement in most aspects of hand-washing technique in the postintervention stage. The health care–associated infection rate decreased from 11.3 to 6.2 per 1000 patient-days.
Conclusion. A problem-based and task-orientated education program can improve hand hygiene compliance. Enhancement of minimal handling and clustering of nursing procedures reduced the total patient contact episodes, which could help to overcome the major barrier of time constraints. A concurrent decrease in health care–associated infection rate and increase in hand hygiene compliance was observed in this study. The observational study could form part of an ongoing audit to provide regular feedback to HCWs to sustain the compliance.
5‐azacytidine supports the long‐term repopulating activity of cord blood CD34+ cells
Authors: Suzuki Motoyuki , Harashima Akira , Okochi Ayumi , Yamamoto Mayuko , Nakamura Shuji , Motoda Ryuichi , Yamasaki Fumiyuki , Orita Kunzo 
Published: October 2004

AbstractDNA methylation plays important roles in a wide range of biological phenomena, especially in the embryonic development and tumorigenesis. However, correlations between differentiation and DNA methylation have not been clarified well in each differentiation system. In this study, we focused our attention on regulatory roles of DNA methylation in normal hematopoietic differentiation using a demethylating reagent, 5‐azacytidine (5‐AzaC). As a source of hematopoietic progenitor cells, we used CD34+ cells prepared from human umbilical cord blood and examined the effects of 5‐AzaC on the colony‐forming activity and the long‐term culture‐initiating (LTC‐IC) activity of these cells. 5‐AzaC treatment increased LTC‐IC frequency 1.57‐ to 2.50‐fold as compared to the nontreated control. In parallel to this, immunoblotting analysis showed that the intensity of overall DNA methylation decreased after 5‐AzaC treatment. These results indicated the involvement of DNA methylation and demethylation in controlling immaturity of hematopoietic progenitor cells and the usefulness of 5‐AzaC for regulating this immaturity. Am. J. Hematol. 77:313–315, 2004. © 2004 Wiley‐Liss, Inc.
Sickle cell crisis associated with hemophagocytic lymphohistiocytosis
Authors: Kio Ebenezer , Onitilo Adedayo , Lazarchick John , Hanna Maged , Brunson Chris , Chaudhary Uzair 
Published: October 2004

AbstractSickle‐beta+ (β+) thalassemia is a double heterozygous genetic disorder characterized by both a qualitative and quantitative abnormality. We present a case of an African American male who was first diagnosed with sickle cell disease (SCD) at the age 23 years when he presented with generalized bone pain, fever, and hepatosplenomegaly. Laboratory findings included thrombocytopenia, microcytic anemia, and markedly elevated ferritin. He was subsequently diagnosed with a sickle‐beta thalassemia hemoglobinopathy. Findings in the bone marrow aspirate and biopsy were consistent with hemophagocytic lymphohistiocytosis (HLH). HLH resolved with the resolution of sickle cell bone pain crisis without use of immunosuppressive therapy. To the best of our knowledge this is the first documented case of HLH associated with sickle cell bone pain crisis. Am. J. Hematol. 77:229–232, 2004. © 2004 Wiley‐Liss, Inc.
Morphological variation and airflow dynamics in the human nose
Authors: Churchill Steven E. , Shackelford Laura L. , Georgi J. Nicole , Black Michael T. 
Published: October 2004

AbstractAirflow dynamics are recognized as being important to the functioning of the human nose in conditioning and filtering inspired air, yet these dynamics are poorly understood. Despite considerable research on airflow dynamics by otolaryngologists, respiratory physiologists, and toxicologists, major disagreements remain about the nature of airflow in the human nose. Specifically, there is little consensus about the character of nasal airflow regimes (laminar or turbulent) and about the major pathways of airflow through the internal chamber. Additionally, a number of features in the human nose have been argued to enhance airflow turbulence, thus increasing the exposure of moving air to the nasal mucosa and facilitating heat and moisture exchange in cold and/or dry climates. These features include: an inferior orientation of the nares; a nasal sill that is high relative to the floor of the internal nasal chamber; a nasal valve that is small in cross‐sectional area relative to that of the internal chamber; and large, projecting conchae. The claim that these features affect airflow dynamics has never been tested. To clarify the nature of human nasal airflow and to test these claims of functional significance to nasal variation, we studied airflow across physiological flow rates using water and dye flowing through anatomically accurate acrylic models of human nasal air passageways (with adjustment of water flow rates to maintain dynamic similarity). The models were derived from direct casting of the nasal passageways of 10 Caucasian (“leptorrhine”) cadavers (six male, four female). Measures of naris angle, nasal sill height, nasal valve area relative to internal chamber cross‐sectional area, and relative projection of the inferior and middle turbinates were taken directly on the resulting casts. The relationships between aspects of nasal morphology and turbulent air flow were evaluated by examining the flow regimes (laminar, semiturbulent, or turbulent) at varying flow rates, with the expectation that the greater the development of the proposed turbulence‐enhancing features the slower the flow rate at which flow would shift from one regime to another. Flow characteristics (both flow regimes and principal pathways) were highly variable within our sample. The relative projection of the inferior turbinate was the only variable that significantly affected the flow rate at which flow became turbulent. However, more projecting turbinates appear to laminate flow rather than to induce turbulence. Nostril orientation was moderately correlated with flow dynamics (with more inferiorly directed nares producing turbulence at slower flow rates), but this correlation was not statistically significant. Relative nasal valve area and nasal sill height were unrelated to turbulence in our models. Am. J. Hum. Biol. 16:625–638, 2004. © 2004 Wiley‐Liss, Inc.
Exploring northeast African metric craniofacial variation at the individual level: A comparative study using principal components analysis
Authors: Keita S.O.Y. 
Published: October 2004

AbstractA principal components analysis was carried out on male crania from the northeast quadrant of Africa and selected European and other African series. Individuals, not predefined groups, were the units of study, while nevertheless keeping group membership in evidence. The first principal component seems to largely capture “size” variation in crania from all of the regions. The same general morphometric trends were found to exist within the African and European crania, although there was some broad separation along a cline. Anatomically, the second principal component captures predominant trends denoting a broader to narrower nasal aperture combined with a similar shape change in the maxilla, an inverse relation between face–base lengths (“projection”) and base breadths, and a decrease in anterior base length relative to base breadth. The third principal component broadly describes trends within Africa and Europe: specifically, a change from a combination of a relatively narrower face and longer vault, to one of a wider face and shorter vault; it shows the northeast quadrant Africans along a cline with the other Africans. Stated in relative terms, the northeastern Africans tend to exhibit narrower bases in relationship to more projecting faces, and broader nasal areas than Europeans, although there is range of variation. Relative to the other African groups, they have narrower nasal areas and narrower faces in relationship to vault length. The crania from the northeast quadrant of Africa collectively demonstrate the greatest pattern of overlap with both Europeans and other Africans. Variation was found to be high in all series but greatest in the African material as a whole. Individuals from different geographical regions frequently plotted near each other, revealing aspects of variation at the level of individuals that is obscured by concentrating on the most distinctive facial traits once used to construct “types.” The high level of African interindividual variation in craniometric pattern is reminiscent of the great level of molecular diversity found in Africa. These results, coupled with those of Y chromosome studies, may help generate hypotheses concerning the length of time over which recent craniometric variation emerged in Africa. Am. J. Hum. Biol. 16:679–689, 2004. © 2004 Wiley‐Liss, Inc.
Origin and evolution of large brains in toothed whales
Authors: Marino Lori , McShea Daniel W. , Uhen Mark D. 
Published: October 2004

AbstractToothed whales (order Cetacea: suborder Odontoceti) are highly encephalized, possessing brains that are significantly larger than expected for their body sizes. In particular, the odontocete superfamily Delphinoidea (dolphins, porpoises, belugas, and narwhals) comprises numerous species with encephalization levels second only to modern humans and greater than all other mammals. Odontocetes have also demonstrated behavioral faculties previously only ascribed to humans and, to some extent, other great apes. How did the large brains of odontocetes evolve? To begin to investigate this question, we quantified and averaged estimates of brain and body size for 36 fossil cetacean species using computed tomography and analyzed these data along with those for modern odontocetes. We provide the first description and statistical tests of the pattern of change in brain size relative to body size in cetaceans over 47 million years. We show that brain size increased significantly in two critical phases in the evolution of odontocetes. The first increase occurred with the origin of odontocetes from the ancestral group Archaeoceti near the Eocene‐Oligocene boundary and was accompanied by a decrease in body size. The second occurred in the origin of Delphinoidea only by 15 million years ago. © 2004 Wiley‐Liss, Inc.
D‐methylphenidate and D,L‐methylphenidate are not developmental toxicants in rats and rabbits
Authors: Teo Steve K. , Stirling David I. , Hoberman Alan M. , Christian Mildred S. , Thomas Steve D. , Khetani Vikram D. 
Published: October 2004

AbstractBACKGROUND: D,L‐threo‐Methylphenidate (D,L‐MPH) is marketed currently for attention deficit hyperactivity disorder in children. D‐threo‐methylphenidate (dexmethylphenidate; D‐MPH) is a refined formulation of D,L‐methylphenidate containing only the active enantiomer and was recently approved in the U.S. for the same condition. D‐Methylphenidate has been shown to be efficacious in patients at half the dose of D,L‐MPH with a potentially improved therapeutic profile. The developmental toxicity of both compounds was determined and compared in rats and rabbits according to current International Conference on Harmonization (ICH) guidelines. METHODS: Groups of pregnant rats were orally dosed twice daily 6 hr apart from Days 7 to 17 of presumed gestation (DG 7–17) for total daily doses of 2, 6 and 20 mg/kg D‐MPH and 40 mg/kg D,L‐MPH. Groups of presumed pregnant rabbits were similarly dosed from DG 6 to 18 for total daily doses of 4, 20 and 100 mg/kg D‐MPH and 200 mg/kg D,L‐MPH. Control groups for both studies were given water vehicle. Comprehensive clinical and developmental measurements were made. Satellite groups of animals were included in the main rat and rabbit studies for toxicokinetic assessment. RESULTS: No drug‐related mortality was seen in the F0 rats and rabbits. The number of rats with repetitive pawing, dilated pupil and aggression was significantly greater for the 40 mg/kg D,L‐MPH compared to the 20 mg/kg D‐MPH dosed rats. Maternal body weight and body weight gain were significantly reduced for both D‐MPH and D,L‐MPH groups compared to control. Maternal reproductive and litter parameters were unaffected by both drugs. No gross external, soft tissue, or skeletal alterations related to both compounds were seen in the fetuses. In rabbits, head‐bobbing and hyperpnea were significantly greater for the 200 mg/kg D,L‐MPH compared to 100 mg/kg D‐MPH. No other maternal or fetal effects related to both compounds were seen. Exposure to D‐MPH (as assessed by AUC) showed no teratogenic effects at exposures of up to 5.6 and 1.7 times for the rat and rabbit respectively compared to children taking the maximum therapeutic dose of 20 mg/day (10 mg twice a day). No teratogenic effects were seen for D,L‐MPH in rat and rabbit at exposures of up to 3.7 to 11.7 times that of the maximum therapeutic pediatric dose of 60 mg/day. CONCLUSIONS: Rats and rabbits dosed with D,L‐MPH exhibited significantly greater incidence of maternal clinical observations at twice the dose of D‐MPH. Both D‐MPH and D,L‐MPH were not teratogenic in rats and rabbits at higher exposure levels compared to humans. © 2003 Wiley‐Liss, Inc.
Microcomputed tomography imaging of skeletal development and growth
Authors: Guldberg Robert E. , Lin Angela S.P. , Coleman Rhima , Robertson Galen , Duvall Craig 
Published: October 2004

AbstractSkeletogenesis is an exquisitely orchestrated and dynamic process, culminating in the formation of highly variable and complex mineralized structures that are optimized for their function. While cellular and molecular biology studies have provided tremendous recent progress toward understanding how patterns of bone formation are regulated, high resolution imaging techniques such as microcomputed tomography (micro‐CT) can provide complementary quantitative information about the progressive changes in three‐dimensional (3‐D) skeletal morphology and density that occur during early skeletal development and postnatal growth. Furthermore, recently developed in vivo micro‐CT systems promise to be a powerful and efficient tool for noninvasively monitoring normal skeletogenesis, as well as for evaluating the effects of genetic or environmental manipulation. This review focuses on the use of micro‐CT imaging and analysis to better understand normal and abnormal skeletal development and growth. Birth Defects Research (Part C) 72: 250–259, 2004. © 2004 Wiley‐Liss, Inc.
Making the mouse embryo transparent: Identifying developmental malformations using magnetic resonance imaging
Authors: Schneider Jürgen E. , Bhattacharya Shoumo 
Published: October 2004

AbstractDevelopmental malformations are a major cause of childhood mortality and are typically characterized by lesions that allow survival of the embryo through gestation. The genetics of developmental malformations are powerfully studied by using high‐throughput, phenotype‐driven screens (e.g., following zebrafish or mouse mutagenesis) or by genotype‐driven studies using transgenic or knockout mice. With regard to either approach, the mouse is anatomically and phylogenetically closer to humans than any other genetically tractable model organism. This is particularly important in the cardiovascular and respiratory systems, which have unique mammalian features. The identification of murine models of developmental malformations is, however, hindered by the opacity of the late gestational mouse embryo. In this review, we describe recent advances in magnetic resonance imaging that make it possible to rapidly identify malformations in the developing mouse embryo with high efficiency. Birth Defects Research (Part C) 72:241–249, 2004. © 2004 Wiley‐Liss, Inc.
Molecular imaging of the embryonic heart: Fables and facts on 3D imaging of gene expression patterns
Authors: Ruijter Jan M. , Soufan Alexandre T. , Hagoort Jaco , Moorman Antoon F.M. 
Published: October 2004

AbstractMolecular imaging, which is the three‐dimensional (3D) visualization of gene expression patterns, is indispensable for the study of the function of genes in cardiac development. The instrumentation, as well as the development of specific contrast agents for molecular imaging, has shown spectacular advances in the last decade. In this review, the spatial resolutions, contrast agents, and applications of these imaging methods in the field of cardiac embryology are discussed. Apart from 3D reconstructions from histological sections, not many of these methods have been applied in embryological research. This review shows that, for most methods, neither the spatial resolutions nor the specificity and applicability of the contrast agents are adequate for the reliable imaging of specific gene expression at the microscopic resolution required for embryological studies of small organs like the developing heart. Although a 3D reconstruction from sections will always suffer from imperfections, the resulting reconstructions meet the aim of most biological studies, especially since the original microscopic images are linked. With respect to imaging of gene expression, only histological sections and laser scanning microscopy provide the required resolution and specificity at the tissue and cellular level. Episcopic fluorescence image capturing and optical projection tomography are being used for microscopic phenotyping and lineage analysis, and both show potential for detailed molecular imaging. Other methods can be used very efficiently in rapid evaluation of biological experiments and high‐throughput screens of large‐scale gene expression profiling efforts when high spatial resolution is not required. Birth Defects Research (Part C) 72:224–240, 2004. © 2004 Wiley‐Liss, Inc.
Current standards of surgery for pancreatic cancer
Authors: Alexakis N , Halloran C , Raraty M , Ghaneh P , Sutton R , Neoptolemos J P 
Published: October 2004

AbstractBackgroundPancreatic cancer carries a dismal prognosis but there has been a vast increase in evidence on its management in the past decade.MethodsAn electronic and manual search was performed for articles on the surgical treatment of pancreatic cancer published in the past 10 years.ResultsSix major areas of advancement were identified. Groups at high risk of developing pancreatic cancer, notably those with chronic pancreatitis and hereditary pancreatitis, have been defined, raising the need for secondary screening. Methods of staging pancreatic cancer for resection have greatly improved but accuracy is still only 85–90 per cent. Pylorus-preserving partial pancreatoduodenectomy without extended lymphadenectomy is the simplest procedure; it does not compromise long-term survival. Adjuvant chemotherapy significantly improves long-term survival. Patients who are free from major co-morbidity have better palliation by surgery (with a double bypass) than by endoscopy. High-volume centres improve the results of surgery for all outcome measures including long-term survival.ConclusionThe surgical management of pancreatic cancer has undergone a significant change in the past decade. It has moved away from no active treatment. The standard of care can now be defined as potentially curative resection in a specialist centre followed by adjuvant systemic chemotherapy.
Intra-abdominal hypertension and the abdominal compartment syndrome (Br J Surg 2004; 91: 1102–1110)
Authors: Teubner A , Anderson I D , Scott N A , Carlson G L 
Published: October 2004

Abstract
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