bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms underlying thrombocytopenia in the neonatal intensive care unit
Authors: Sola MC , Rimsza LM 
Published: August 2010

Thrombocytopenia is one of the most common hematological problems among neonates in the neonatal intensive care unit (NICU), but in the majority of cases the kinetic mechanism responsible is unclear. This review focuses on both traditional and innovative methods used to evaluate the mechanisms responsible for thrombocytopenia in neonates, and analyzes the data generated from those methods. Conclusion: Results of studies using new methods for evaluating thrombocytopenia, coupled with recent descriptions of marrow megakaryocyte mass, suggest that decreased platelet production complicates most cases of thrombocytopenia among neonates in the NICU.
Use of the bleeding time in the neonatal intensive care unit
Authors: Vecchio A Del 
Published: August 2010

Impairments of primary hemostasis are frequently responsible for serious bleeding in sick infants in the neonatal intensive care unit (NICU). Therefore, a rational approach to these infants with hemorrhagic manifestations, in addition to an accurate medical history, a careful physical examination and routine screening coagulation tests, may include a bleeding time. The bleeding time is the traditional in vivo test for assessing primary hemostasis. It is a useful clinical tool to detect quantitative or qualitative platelet disorders or microvascular defectiveness. Its diagnostic value in neonates is controversial, mainly owing to limited experience in executing the test, which is performed uncommonly in the NICU. Using a template device expressly adapted for neonates (Surgicutt Newborn), a small incision 2.5 mm long and 0.5 mm deep provides a standardized, reproducible and sensitive bleeding time, with minimal scarring and pain. Various hereditary or acquired maternal and neonatal diseases, as well as some antepartum medications given to the mother or drugs commonly used to treat NICU patients, such as indomethacin, ibuprofen, penicillin compounds and theophylline, can impair primary hemostasis and consequently prolong the bleeding time in neonates. Furthermore, other factors distinctive to neonates, including gestational age, the increased von Willebrand factor concentration and function, high hematocrit, the large size of erythrocytes and platelet hyporeactivity in the first 10 d of life, affect plateletvessel wall interaction and influence the interpretation of bleeding time results in newborn infants. Because the clinical evaluation of primary hemostasis consists of complex laboratory testing, largely reserved for specialized laboratories and currently not routinely performed in newborn infants, automated bleeding time devices specifically generated to make standardized and acceptably small incisions in newborn infants have become a surrogate. Conclusion: With awareness of its value and limitations, the bleeding time can be included in the baseline evaluation of neonates in the NICU, for guiding diagnosis and treatment of primary hemostatic disorders.
What is the rationale for the use of granulocyte and granulocyte‐macrophage colony‐stimulating factors in the neonatal intensive care unit
Authors: La Gamma EF , De Castro MH 
Published: August 2010

Neonatal sepsis remains an unsolved major contributor to morbidity and mortality. In the 1980s the promise of augmenting immune function using pooled intravenous gammaglobulin to supplement the exceedingly low levels of immunoglobulin G in premature infants failed to demonstrate a clear advantage. Similarly, cytokine augmentation of cellular function in the 1990s largely appeared to be suffering the same fate. However, both results may arise from a problem in experimental design where the combination of both treatments may be necessary along with specific antibody. For example, in vitro, independently of an array of other humoral and cellular immature immune system issues, opsonization of bacteria is improved in the presence of antibody. The question is whether the same result can be achieved in vivo. No experiments have been reported that directly test this hypothesis. Conclusion: More investigation is needed in this challenging area of neonatal research.
Perinatal aspects of iron metabolism
Authors: Rao R , Georgieff MK 
Published: August 2010

Iron sufficiency is critical for rapidly developing fetal and neonatal organ systems. The majority of iron in the third trimester fetus and the neonate is found in the red cell mass (as hemoglobin), with lesser amounts in the tissues as storage iron (e.g. ferritin) or functional iron (e.g. myoglobin, cytochromes). Iron is prioritized to hemoglobin synthesis in red cells when iron supply does not meet iron demand. Thus, non‐heme tissues such as the skeletal muscle, heart and brain will become iron deficient before signs of iron‐deficiency anemia. Gestational conditions that result in lower newborn iron stores include severe maternal iron deficiency, maternal hypertension with intrauterine growth retardation and maternal diabetes mellitus. Stable, very low birthweight premature infants are also at risk for early postnatal iron deficiency because they accrete less iron during gestation, grow more rapidly postnatally, are typically undertreated with enteral iron and receive fewer red cell transfusions. Conversely, iron overload remains a significant concern in multiply transfused sick preterm infants because they have low levels of iron‐binding proteins and immature antioxidant systems. Conclusion: The highly variable iron status of preterm infants combined with their risk for iron deficiency and toxicity warrants careful monitoring and support in the newborn and postdischarge periods.SummaryIron metabolism undergoes major changes during the last trimester and early postnatal period, at a time when the infant is particularly sensitive to both iron deficiency and iron overload. Various prenatal conditions affect the iron load at birth, including maternal iron deficiency, maternal hypertension with fetal growth restriction, maternal diabetes mellitus and preterm delivery. Since iron is prioritized to red cells in the fetus and neonate, other organs such as the liver, heart and brain can potentially suffer from iron deficiency when iron supply does not meet iron demand. In the postnatal period, the premature infant is placed at earlier risk of iron deficiency because of rapid growth rates, uncompensated iron losses from phlebotomy and low nascent iron stores. Conversely, the immature antioxidant systems and low total iron‐binding capacity of the preterm infant increase the risk of potential toxicity from iron.
New biomarkers of fetal‐neonatal hypoxic stress
Authors: Perrone S , Bracci R , Buonocore G 
Published: August 2010

The complex pathophysiological mechanisms underlying perinatal hypoxia make it difficult to define early markers of severe hypoxia‐ischemia encephalopathy. However, as progress in the development of neuroprotective therapeutic measures continues, the early identification of neonates at risk of severe hypoxic‐ischemic encephalopathy is an important goal for appropriate decision making. Although the timing of perinatal hypoxic brain damage may vary and is sometimes unknown, high levels of non‐protein‐bound iron and high nucleated red blood cell counts in cord blood indicate an antepartum origin of neurological impairment, because they can occur only as a consequence of a pre‐existing asphyxic event. Conclusion: The combined assessment of nucleated red blood cells and non‐protein‐bound iron at birth seems extremely useful for the early identification of newborns at high risk of brain damage. Activin A also seems to be a reliable marker of perinatal hypoxia. Prospective long‐term follow‐up studies are needed to verify their predictive role.
Electrocardiographic signs of hypertrophy in Fabry disease‐associated hypertrophic cardiomyopathy
Authors: Kampmann C , Wiethoff CM , Martin C , Wenzel A , Kampmann R , Whybra C , Miebach E , Beck M 
Published: August 2010

Aims: Fabry disease results from deficient activity of the lysosomal enzyme α‐galactosidase A. Progressive accumulation of the major substrates leads, in both men and women, to progressive hypertrophic cardiomyopathy. We aimed to evaluate the utility of different electrocardiographic (ECG) parameters for assessing the degree and severity of hypertrophic cardiomyopathy in patients with Fabry disease. Methods: A total of 166 ECGs of 94 hemi‐ and heterozygous patients with Fabry disease were analysed and compared with echocardiographic‐estimated left ventricular mass (LVM). Results: There was a significant (p > 0.0001) correlation between QRS duration (R2= 0.59), 12‐lead amplitude/duration product (R2= 0.61), Sokolow‐Lyon voltage/duration product (R2= 0.52) and LVM. Analysis of receiver operating characteristics revealed that the 12‐lead amplitude/duration product had the highest sensitivity‐specificity relationship (p > 0.01 compared with the Cornell index). Conclusion: In general, ECG signs of left ventricular hypertrophy correlated well with LVM as revealed by echocardiography. Of the parameters studied, the 12‐lead amplitude/duration product was the most successful at describing the severity of cardiac involvement in Fabry disease. These data suggest that ECG parameters have potential for use as a simple and cost‐effective means of screening for hypertrophic cardiomyopathy in patients with Fabry disease.
Isolated cardiac manifestations in Fabry disease: the UK experience
Authors: Sachdev B , Elliott PM 
Published: August 2010

Cardiac abnormalities are common in patients with Fabry disease, and may be the only clinical manifestation of the disease in some patients. At St George's Hospital Medical School, a national referral centre for hypertrophic cardiomyopathy in the UK, a study of 153 consecutively referred male patients revealed that 4% had Fabry disease. This increased to 6% in patients over 40 years of age. All these patients had electrocardiographic (ECG) abnormalities, most of which were consistent with those found in patients with classic Fabry disease: left ventricular hypertrophy, repolarization abnormalities and a prolonged QRS complex. A study of heterozygote females with Fabry disease also showed ECG and echocardiographic abnormalities in most patients. Conclusions: Fabry disease should be considered in the differential diagnosis of otherwise unexplained cardiac disease.
Mechanisms of neuropathic pain and their importance in Fabry disease
Authors: Birklein F 
Published: August 2010

One of the most prominent features of Fabry disease is neuropathic pain. Neuropathic pain occurs after neuronal damage. In contrast to inflammatory or trauma‐related pain, which normally helps to maintain or restore body functions, neuropathic pain tends to become chronic, and must therefore be considered a ‘pathological’ pain. Neuropathic pain has usually been classified according to the aetiology of nerve damage: traumatic, inflammatory, cancer‐related or metabolic (e.g. Fabry disease). However, use of this classification often results in inadequate therapy for neuropathic pain. Recent research has revealed distinct mechanisms that are responsible for neuropathic pain. These mechanisms are independent of the aetiology of nerve damage. The most important mechanisms are accumulation and maldistribution of sodium channels on injured axons, pathological sympathoafferent coupling, disinhibition of nociception and central or peripheral nociceptive sensitization. Conclusions: Future research should focus on diagnostic tools to identify the predominant mechanisms in individual patients. These mechanism could be targeted specifically by drugs, or non‐drug therapy, enabling more effective treatment of neuropathic pain.
Evaluation of peripheral and autonomic nerve function in Fabry disease
Authors: Hilz MJ 
Published: August 2010

The neurological manifestations of Fabry disease include severe episodes of lancinating pain and burning paraesthesias in the extremities, often triggered by changes in temperature. The preferential involvement of small nerve fibres and the accumulation of storage product in the central autonomic nervous system and autonomic ganglia means that standard neurophysiological procedures cannot adequately evaluate the peripheral and autonomic nervous systems of affected patients. This paper describes the various methods that have been developed to assess impairment of temperature perception, vibratory perception, sudomotor and sweat gland function, and limb and superficial skin blood flow and vasoreactivity. These methods, including thermal provocation tests, quantitative sudomotor axon reflex testing and venous occlussion plethsmography, have been used effectively in patients with Fabry disease to measure the extent of neurological dysfunction. Conclusions: Effective methods for measuring neurological involvement in patients with Fabry disease have been developed. These methods will be valuable in assessing the response of patients to enzyme replacement therapy.
Pathophysiology and assessment of neuropathic pain in Fabry disease
Authors: Schiffmann R , Scott LJC 
Published: August 2010

Severe neuropathic pain and hypohidrosis are important symptoms of Fabry disease, particularly in the first three decades of life. The pain is associated with a length‐dependent small‐fibre neuropathy that also causes a selective deficiency of cold perception. Cold exposure often accentuates the pain and worsens thermal perception. The hypohidrosis leads to poor exercise and heat tolerance. The mechanisms by which α‐galactosidase A deficiency causes these physiological abnormalities are poorly understood. The stored glycolipid (globotriaosylceramide) may interfere with the function of cellular membrane proteins, such as ion channels, or may lead to cytotoxicity. The characteristic neuropathic pain can be symptomatically treated with various types of anticonvulsant drugs, such as carbamazepine. Improvement in neuropathic pain as a primary outcome measure has been useful in demonstrating that enzyme replacement therapy is effective in improving pain‐related quality of life in Fabry disease. Conclusions: The dysfunction of the peripheral nervous system is easily assessable and more readily reversible with specific therapy than the destructive processes that occur in organs such as the kidney. In future, therefore, it is likely that neuropathic pain, quantitative sensory testing and hypohidrosis will serve as clinical outcome measures for studies of specific and effective therapies for Fabry disease.
Arterial remodelling in Fabry disease
Authors: Boutouyrie P , Laurent S , Laloux B , Lidove O , Grunfeld JP , Germain DP 
Published: August 2010

Aim: The enzymatic defect in Fabry disease results in the slow systemic deposition of uncleaved glycosphingolipids in the lysosomes of vascular endothelium and smooth muscle cells, leading to ischaemic strokes, cardiomyopathy and renal failure. Whereas it is known that Fabry disease affects small blood vessels, little is known about its effects on peripheral large arteries. We therefore set out to compare parameters of arterial wall structure and function in a cohort of patients with Fabry disease and an age‐matched control group. Methods: Large artery phenotype was non‐invasively investigated in 21 hemizygous patients with Fabry disease and 24 age‐matched male controls. Common carotid and radial artery diameter, intima‐media thickness (IMT) and distensibility were determined with high‐definition echotracking systems and aplanation tonometry. Results: Patients with Fabry disease had a significant twofold increase in radial artery IMT and distensibility, independent of body surface area, age and mean blood pressure. In both groups, older age at the time of examination was significantly associated with larger radial artery IMT. The relationship between age and radial IMT was 2.3‐fold higher in patients with Fabry disease than in controls (p > 0.01). Carotid IMT was mildly but significantly increased in patients with Fabry disease (+18%), whereas distensibility was unchanged. Conclusion: This study presents evidence of a major increase in arterial wall thickness and distensibility, measurable at the site of a medium‐sized artery, in a cohort of patients with classic Fabry disease.
Non‐viral transfer approaches for the gene therapy of mucopolysaccharidosis type II (Hunter syndrome)
Authors: Tomanin R , Friso A , Alba S , Puicher E Piller , Mennuni C , Monica N La , Hortelano G , Zacchello F , Scarpa M 
Published: August 2010

Aims: Hunter syndrome is a rare X‐linked lysosomal storage disorder caused by the deficiency of the housekeeping enzyme iduronate‐2‐sulphatase (IDS). Deficiency of IDS causes accumulation of undegraded dermatan and heparan‐sulphate in various tissues and organs. Approaches have been proposed for the symptomatic therapy of the disease, including bone marrow transplantation and, very recently, enzyme replacement. To date, gene therapy strategies have considered mainly retroviral and adenoviral transduction of the correct cDNA. In this paper, two non‐viral somatic gene therapy approaches are proposed: encapsulated heterologous cells and muscle electro‐gene transfer (EGT). Methods: Hunter primary fibroblasts were co‐cultured with either cell clones over‐expressing the lacking enzyme or with the same incorporated in alginate microcapsules. For EGT, plasmid vector was injected into mouse quadriceps muscle, which was then immediately electro‐stimulated. Results: Co‐culturing Hunter primary fibroblasts with cells over‐expressing IDS resulted in a three‐ to fourfold increase in fibroblast enzyme activity with respect to control cells. Fibroblast IDS activity was also increased after co‐culture with encapsulated cells. EGT was able to transduce genes in mouse muscle, resulting in at least a tenfold increase in IDS activity 1–5 weeks after treatment. Conclusion: Although preliminary, results from encapsulated heterologous cell clones and muscle EGT encourage further evaluations for possible application to gene therapy for Hunter syndrome.
Unexplained infant crying: an evolutionary perspective*
Authors: Hofer MA 
Published: August 2010

The absence of adverse health outcomes later in development and the similarity of defining features of “colic” across cultures suggest that an evolutionary perspective may give us some insight into the nature of this puzzling condition. Evidence suggests that the larynx evolved first as a protective valve and later as a means to stabilize the upper thorax momentarily for precision upper arm movements. Recently, we found another physiological role for the larynx in regulating respiratory function to promote the recovery of young rats from severe hypothermia. In the process, bursts of calling were emitted by unconscious pups, which were nevertheless effective in eliciting maternal search and retrieval. These unexpected findings reveal how infant calling may have evolved as a communicative signal derived from more primitive physiological functions of the larynx. Repetitive calling in the normal young rat when isolated from its littermates and mother is regulated by multiple sensory cues present in the infant's social interactions, and in the paper it is described how this sensory input projects to central neuromodulatory systems known to be active in the control of anxiety behaviors in adult rats and humans. Conclusion: This broad range of functions for infant calling in other mammals suggests several new ways to approach the further study and treatment of unexplained crying in human infants.
Plasma total homocysteine increases from day 20 to 40 in breastfed but not formula‐fed low‐birthweight infants
Authors: Fokkema MR , Woltil HA , van Beusekom CM , Schaafsma A , Dijck‐Brouwer DAJ , Muskiet FAJ 
Published: August 2010

Homocysteine is an intermediate in the folate cycle and methionine metabolism. This study investigated whether formula‐fed infants have different plasma total homocysteine to their breastfed counterparts, and during what period any difference developed. Plasma total homocysteine was determined in 53 formula‐fed and 15 breastfed healthy low‐birthweight babies (≫2500 g) around days 10, 20 and 40. Total homocysteine was also measured in human milk. Mean ± SD plasma total homocysteine levels (μmol 1‐1) at days 10, 20 and 40 were 6.4 ± 2.6, 6.7 ± 2.4 and 9.1 ± 2.4 (breastfed), and 7.5 ± 3.2, 7.3 ± 2.1 and 7.4 ± 1.6 (formula‐fed). Homocysteine of breastfed babies at day 40 was higher than that of breastfed babies at day 20 (p > 0.0001), and that of formula‐fed counterparts at day 40 (p= 0.002). Homocysteine correlated negatively with formula (day 10) and breast milk (day 40) volume intakes. Median (range) homocysteine in 12 mature human milk samples was 0.30 (not detectable to 0.7) μmol 1−1. Conclusion: Increasing plasma total homocysteine in breastfed babies to higher levels compared with formula‐fed babies may be caused by a gradually developing suboptimal B‐vitamin status in lactating women.
Impact of topical oils on the skin barrier: possible implications for neonatal health in developing countries
Authors: Darmstadt GL , Mao‐Qiang M , Chi E , Saha SK , Ziboh VA , Black RE , Santosham M , Elias PM 
Published: August 2010

Topical therapy to enhance skin barrier function may be a simple, low‐cost, effective strategy to improve outcome of preterm infants with a developmentally compromised epidermal barrier, as lipid constituents of topical products may act as a mechanical barrier and augment synthesis of barrier lipids. Natural oils are applied topically as part of a traditional oil massage to neonates in many developing countries. We sought to identify inexpensive, safe, vegetable oils available in developing countries that improved epidermal barrier function. The impact of oils on mouse epidermal barrier function (rate of transepidermal water loss over time following acute barrier disruption by tape‐stripping) and ultrastructure was determined. A single application of sunflower seed oil significantly accelerated skin barrier recovery within 1 h; the effect was sustained 5 h after application. In contrast, the other vegetable oils tested (mustard, olive and soybean oils) all significantly delayed recovery of barrier function compared with control‐ or Aquaphor‐treated skin. Twice‐daily applications of mustard oil for 7 d resulted in sustained delay of barrier recovery. Moreover, adverse ultrastructural changes were seen under transmission electron microscopy in keratin intermediate filament, mitochondrial, nuclear, and nuclear envelope structure following a single application of mustard oil.Conclusion: Our data suggest that topical application of linoleate‐enriched oil such as sunflower seed oil might enhance skin barrier function and improve outcome in neonates with compromised barrier function. Mustard oil, used routinely in newborn care throughout South Asia, has toxic effects on the epidermal barrier that warrant further investigation.