bluuebunny/crossref_metadata_2025 huggingface dataset:
Granulocyte Colony-Stimulating Factor, Granulocyte Macrophage Colony-Stimulating Factor and Neutrophils in the Bronchoalveolar Lavage Fluid of Premature Infants with Respiratory Distress Syndrome
Authors: Papoff Paola , Christensen Robert D. , Calhoun Darlene A. , Juul Sandra E.
Published: April 2003

Background: Granulocyte colony-stimulating factor (G-CSF) and granulocyte macrophage colony-stimulating factor (GM-CSF) promote clonal maturation of neutrophil and macrophage progenitors and increase functional activities of mature cells. The number and activity of neutrophils and macrophages in the lung affect healing and remodeling following respiratory distress syndrome (RDS). Questions of the Study: (1) Are G-CSF and GM-CSF present in the airways of preterm neonates with RDS? (2) Do airway G-CSF and GM-CSF concentrations correlate with neutrophil and macrophage number in the bronchoalveolar lavage (BAL) fluid? (3) Are alveolar macrophages a source of airway G-CSF and GM-CSF? (4) Is in vitro expression of G-CSF and GM-CSF by airway macrophages modified by dexamethasone, endotoxin, or hyperoxia? Methods: Eighteen preterm neonates with RDS requiring mechanical ventilation within the first 24 h of life underwent BAL on days 1, 3, 6, 10, 12, 15, 20, and 28 if still intubated. BAL G-CSF and GM-CSF concentrations were measured by ELISA, and neutrophils and macrophages were counted. Alveolar macrophages were cultured, and G-CSF and GM-CSF expression measured in the presence and absence of dexamethasone, endotoxin, and hyperoxia. Results: G-CSF and GM-CSF were present in the BAL of intubated preterm neonates. In infants who did not develop chronic lung disease (CLD) (n = 5), G-CSF and GM-CSF concentrations were highest in the first days of life, falling thereafter, while in those who did develop CLD (n = 13) these concentrations increased over time. Neutrophil concentrations in BAL fluid followed a similar pattern. Macrophages from BAL were identified as a source of G-CSF and GM-CSF mRNA and protein. G-CSF and GM-CSF expression by these macrophages was increased by endotoxin, decreased by dexamethasone, and unchanged by hyperoxia. Conclusions: G-CSF and GM-CSF are present in neonatal BAL, and may contribute significantly to the accumulation of alveolar neutrophils.
Once-a-Day Individualized Amikacin Dosing for Suspected Infection at Birth Based on Population Pharmacokinetic Models
Authors: Labaune J.M. , Bleyzac N. , Maire P. , Jelliffe R.W. , Boutroy M.J. , Aulagner G. , Putet G.
Published: April 2003

Amikacin is widely used in the treatment of suspected or confirmed neonatal infections. However, dosage regimens are not well defined in this group of patients because of a wide inter-individual pharmacokinetic variability. An individualized goal-oriented amikacin dosage design was applied using population pharmacokinetic data. A dosing chart was developed for neonates during the first 2 days of life, by using population pharmacokinetic parameter values and USCPACK software. This dosing chart based on gestational age (GA) and body weight gives a once-a-day amikacin dosage regimen involving an injection every 24 h. Validation was performed in 57 neonates less than 2 days old, divided into three GA groups and prospectively treated using the dosing chart. Target peak serum levels of amikacin were obtained in 62–80% of patients after the first dose and in 80–100% after the second dose, and trough concentrations were obtained in 100%. This study has confirmed the need for individualization of amikacin dosage regimens in neonates.
Prophylactic Effects of Recombinant Human Superoxide Dismutase in Neonatal Lung Injury Induced by the Intratracheal Instillation of Endotoxin in Piglets
Authors: Nakamura Toshihiko , Ogawa Yunosuke
Published: April 2003

The efficacy of prophylactic endotracheal administration of superoxide dismutase (SOD) was assessed in an animal model of acute lung injury induced by intratracheal endotoxin in neonatal piglets. Twenty-one anesthetized piglets were studied and underwent mechanical ventilation. The animals received recombinant human SOD (5 or 20 mg/kg intratracheally) 10 min before induction of acute lung injury with intratracheal endotoxin (20 mg/kg). The PaO2 values of the SOD-treated group remained higher than that of the control group until the end of the experiment. In contrast, the PaCO2 values remained lower. Lung compliance remained higher. Thiobarbituric acid-reactive substances and albumin levels in the broncho-alveolar lavage fluid were more significantly increased in controls. Histologic examination showed that the degrees of atelectasis and edema in the SOD treatment group were milder than those of the control group. Thus, the present findings suggest that prophylactic treatment with SOD may be, at least in part, effective for alleviating acute lung injury caused by endotoxins.
Iron-Deficient Erythropoiesis in Neonatal Rats
Authors: Dubuque Suzanne H. , Dvorak Bohuslav , Woodward Suann S. , McCuskey Robert S. , Kling Pamela J.
Published: April 2003

Anemia in premature infants is extremely common. Precise quantitation of iron status and determination of iron incorporation into erythrocytes are important in monitoring therapy for anemia in premature infants, especially when treating with recombinant human erythropoietin (rhEPO). However, the traditional indices of the iron status have limited usefulness in this population. The goal of the current work is to develop an experimental animal model system that addresses the clinical issue relating to quantitation of iron delivery to erythrocytes. We first determined normal hematological values for nontreated, dam-suckled Sprague-Dawley rats by measuring markers of erythropoiesis and iron status during the first 12 postnatal days (PND). The experimental group of rats were administered parenteral rhEpo (430 IU·kg–1 · day–1) for 8 days (from PND 4 until PND 12) in the absence (rhEpo–Fe) or presence (rhEpo+Fe) of oral iron supplementation (6 mg·kg–1·day–1). Rat pups receiving oral iron only (control+Fe) and pups that were sham fed with the orogastric tube (control–Fe) were included as controls. Hematological parameters were measured in blood and bone marrow. In a pattern similar to that seen in premature infants during the first 2 months of life, the levels of these hematopoietic markers were dynamic and changed during the first 12 PND. After challenging experimental animals with subcutaneous rhEpo, evidence of iron-deficient erythropoiesis was seen in the rhEpo–Fe group. Red blood cell levels and absolute reticulocyte counts were higher in both groups receiving rhEpo as compared with the controls. However, the rhEpo–Fe group experienced a lower hemoglobin level, a lower mean red cell volume, a greater red cell distribution width, and a higher zinc protoporphyrin/heme (ratio than the rhEpo+Fe group. The neonatal rat is an excellent model of iron-deficient erythropoiesis and will be useful in designing future mechanistic studies examining the interplay between iron and erythropoiesis in the anemic, iron-challenged premature neonate.
In utero Exposure to Immunosuppressive Drugs
Authors: Prévot Anne , Martini Stephan , Guignard Jean-Pierre
Published: April 2003

The number of pregnant women receiving immunosuppressants for anti-rejection therapy or autoimmune diseases is increasing. All immunosuppressive drugs cross the placenta, raising questions about the long-term outcome of the children exposed in utero. There is no higher risk of congenital anomalies. However, an increased incidence of prematurity, intrauterine growth retardation (IUGR) and generally low birth weight has been reported, as well as maternal hypertension and preeclampsia. The most frequent neonatal complications are those associated with prematurity and IUGR, as well as adrenal insufficiency with corticosteroids, immunological disturbances with azathioprine and cyclosporine, and hyperkalemia with tacrolimus. The long-term follow-up of infants exposed to immunosuppressants in utero is still limited and experimental studies raise the question whether there could be an increased incidence at adult age of some pathologies including renal insufficiency, hypertension and diabetes.
Race, Candida Sepsis, and Retinopathy of Prematurity
Authors: Tadesse Misrak , Dhanireddy Ramasubbareddy , Mittal Mahdur , Higgins Rosemary D.
Published: April 2003

The objective of this observational cohort study at Georgetown University Hospital from January 1, 1994 through December 31, 1997 was to investigate race, Candida sepsis, and duration of oxygen exposure in infants with retinopathy of prematurity (ROP) with birth weight ≤1,000 g. The incidence of ROP was 70.8% (114/161). The incidence of stage III or greater ROP in the Caucasian infants was significantly higher at 46.7% (14/30) than in the African-American infants at 23.8% (20/84) with p < 0.02. In addition, the incidence of threshold disease was higher in Caucasian infants 33.3% (10/30) when compared to African-American infants 9.5% (8/84) with p < 0.002. Using multiple logistic regression, African-American race was found to be an independent protective factor against developing severe ROP [adjusted odds ratio 0.39; 95% confidence interval (UCI) 0.16–0.97]. Extremely-low-birth-weight African-American infants with comparable severity of illness (including birth weight, gestational age, duration of supplemental oxygen exposure, and Candida sepsis) are less likely to develop severe ROP than Caucasian infants.
Meconium Enhances the Release of Nitric Oxide in Human Airway Epithelial Cells
Authors: Khan Amir M. , Lally Kevin P. , Elidemir Okan , Colasurdo Giuseppe N.
Published: April 2003

Meconium aspiration syndrome (MAS) is a cause of significant morbidity and mortality in the perinatal period. Despite the clinical relevance of MAS, its pathogenesis is poorly understood and the role played by epithelial-derived metabolites not well defined. In this study, we evaluated whether exposure to meconium affects the release of nitric oxide production in human airway epithelial cells. Monolayers of A549 cells, a transformed human epithelial cell line, were incubated with various concentrations of meconium. Control cells were incubated with serum-free medium in a similar manner. The supernatant fluid was removed at various time points and assayed for nitrite production. In selected experiments, the effects of dexamethasone (10–6 M), L-nitroarginine methyl ester (L-NAME, 10–6 M) and indomethacin (10–6 M) on nitrite release were evaluated. Results were obtained in terms of pmol/mg protein and expressed as % control (mean ± SE). We found exposure to meconium produced a significant release of nitrite from A549 cells. Dexamethasone, L-NAME and indomethacin inhibited meconium-induced release of nitrite. Our findings demonstrate meconium enhances the production of nitric oxide from A549 cells suggesting that airway epithelial cells and their metabolic products may play an important role in the pathogenesis of MAS.
Plasma and Urine Elastase Alpha-1-Proteinase Inhibitor Levels in Neonatal Urinary Tract Infection
Authors: Bakakos P. , Messaritaki A. , Mandyla H. , Nicolaidou P. , Anagnostakis D.
Published: April 2003

Objective: To examine whether plasma or urine elastase α1-proteinase inhibitor (E-α1-PI) levels could be used as a diagnostic marker of urinary tract infection (UTI) in neonates. Subjects and Methods: Plasma and urine E-α1-PI levels were measured by immunoassay in 23 neonates with UTI at the time of admission and 72 h after the onset of treatment and in 10 ‘normal’ neonates (i.e. with trivial problems). Additionally E-α1-PI plasma levels were measured in 15 neonates with septicemia. Results: E-α1-PI plasma levels did not differ between normal neonates and those with UTI. Urine E-α1-PI levels were significantly higher in neonates with UTI on admission compared to normal neonates. A significant decrease in urine E-α1-PI levels was noticed 72 h after the onset of treatment in all but 2 neonates in whom infection persisted. In this study, we have found that the urine E-α1-PI concentration at a cutoff level of 48 µg/l had a sensitivity of 83%, a specificity of 90%, a positive predictive value of 95% and a negative predictive value of 69% for the diagnosis of neonatal UTI. Conclusion: Elevated levels of E-α1-PI in urine seem to be a useful tool for the diagnosis of UTI in neonates (even in those that have already been started on antibiotics) and possibly a valuable marker for early recognition of treatment failure.
Ontogeny of Endothelin-Converting Enzyme Gene Expression and Protein Content in the Ovine Fetal Lung
Authors: Ivy Dunbar , Tanzawa Kazuhiko , Abman Steven H.
Published: April 2003

Endothelin 1 (ET-1) is a potent vasoconstrictor and smooth muscle comitogen that is produced by endothelin-converting enzyme 1 (ECE-1) in endothelium and smooth muscle of the vascular wall in adult pulmonary arteries. However, little is known about the role of ECE-1 in the fetal pulmonary circulation. The ET-1 protein content falls just prior to birth in the fetal lamb lung. We hypothesized that the expression of ECE-1 is developmentally regulated and that ECE-1 levels fall prior to birth. To test this hypothesis, we measured lung ECE-1 mRNA levels and protein content and determined the cellular localization of ECE-1 expression in lung tissues from fetal lambs between 70 and 140 days of gestation (term = 145 days), newborn lambs, and ewes. We found that ECE-1 mRNA expression and protein content were lower in the fetal lamb lung just prior to birth in comparison with the newborn lamb lung. Immunolocalization of ECE-1 protein showed expression of ECE-1 in the vascular endothelium but not in the vascular smooth muscle at all gestational ages. We conclude that ECE-1 is developmentally regulated and that ECE-1 is expressed in the vascular endothelium but not in the smooth muscle of the fetal pulmonary vasculature. We speculate that alterations in ECE-1 contribute to the changes in ET-1 levels during the perinatal period and that the majority of ET-1 produced in the fetal lamb pulmonary vasculature is produced by the vascular endothelium.
Sensory Brain Areas in Mesopelagic Fishes
Authors: Wagner H.-J.
Published: April 2003

Four areas of the brain that receive primary projections from chemical senses ([1] olfactory bulb, [2] facial and vagal lobes), the eye ([3] optic tectum), and somato- and mechanosensory systems such as the lateral line, vestibular and auditory systems ([4] trigeminal and octavolateral regions) have been studied and relative size differences used to deduce the sensory specializations of 67 species of mesopelagic fishes. One type of analysis used the average relative volumes of brain areas and identified ‘specialists’ with only one brain area above-average (36%), species ‘dominated’ by two sensory brain regions (49%), and generalists (15%), with three areas above-average. In addition, a cluster analysis was performed that separated 49 species which were mostly visually oriented from 18 non-visual species, among which 16 were characterized by an association of above-average trigeminal/octavolateral and gustatory areas, and a single species with a dominant olfactory bulb. The results support the idea that these species occupy a rich sensory environment for which the absence of sunlight is compensated by chemical and mechanosensory stimuli as well as by bioluminescent signals. This has lead to the development of specializations for the perception of single stimulus-modes, most notably for the visual system, as well as for combinations of various receptors and central processing areas, with a preference for associating either the chemical senses, including the olfactory and facial/vagal systems, or the trigeminal/octavolateral systems.
Microanatomy of Facial Vibrissae in the Florida Manatee: The Basis for Specialized Sensory Function and Oripulation
Authors: Reep R.L. , Stoll M.L. , Marshall C.D. , Homer B.L. , Samuelson D.A.
Published: April 2003

Sirenians, including Florida manatees, possess an array of hairs and bristles on the face. These are distributed in a pattern involving nine distinct regions of the face, unlike that of any other mammalian order. Some of these bristles and hairs are known to be used in tactile exploration and in grasping behaviors. In the present study we characterized the microanatomical structure of the hair and bristle follicles from the nine regions of the face. All follicles had the attributes of vibrissae, including a dense connective tissue capsule, prominent blood sinus complex, and substantial innervation. Each of the nine regions of the face exhibited a distinct combination of these morphological attributes, congruent with the previous designation of these regions based on location and external morphological criteria. The present data suggest that perioral bristles in manatees might have a tactile sensory role much like that of vibrissae in other mammals, in addition to their documented role in grasping of plants during feeding. Such a combination of motor and sensory usages would be unique to sirenians. Finally, we speculate that the facial hairs and bristles may play a role in hydrodynamic reception.
Evolution of Calls and Auditory Tuning in the Physalaemus pustulosus Species Group
Authors: Wilczynski Walter , Rand A. Stanley , Ryan Michael J.
Published: April 2003

In species within the Physalaemus pustulosus species group, male frogs produce a whine-like advertisement call consisting of a frequency sweep typically descending from 1,000 to 400 Hz (depending on the species). One species, Physalaemus pustulosus, the túngara frog, has evolved a second call syllable, the chuck, which males place after their whine. Most energy in the chuck is above 1,500 Hz and peaks at 2,400 Hz. We investigated whether the evolution of this new call component in P. pustulosus coincided with evolution of auditory tuning. We used multiunit electrophysiological recordings of auditory-evoked activity in the midbrain to characterize auditory tuning in Physalaemus pustulosus, four other Physalaemus species within the P. pustulosus clade, and three additional, closely related Physalaemus species as outgroups. All eight species had similar sensitivity profiles, with a broad area of enhanced sensitivity from 100 to 1,100 Hz, which we presume represents amphibian papilla (AP) tuning, and a second, narrower area of enhanced sensitivity centered above 2,100 Hz, which we presume represents basilar papilla (BP) tuning. For all species, the whine stimulates the AP. The P. pustulosus chuck stimulates the BP. The frequency with greatest AP sensitivity differed significantly among species. Although in all cases the AP peak lay within the frequency sweep of the whine, phylogenetically corrected correlations revealed no significant relationships between AP tuning and any spectral feature of the whine. BP tuning was similar among all species, with mean BP best excitatory frequencies (BEFs) around 2,100–2,200 Hz, with the exception of P. pustulatus, with a mean BP BEF of 2,549 Hz. Physalaemus pustulosus, the only investigated species that produces a call component stimulating the BP, had a BP BEF that was not significantly different from any of the species within its clade except P. pustulatus, or from any of the outgroup species. A phylogenetic reconstruction of ancestral BP tuning confirms that the only point of evolutionary change in BP tuning is in the line of descent leading to P. pustulatus, not in the line leading to P. pustulosus despite this being the species using the BP for communication. The results indicate that BP tuning around 2,200 Hz is a conserved trait in the Physalaemus pustulosus species group and that no evolution of BP tuning accompanied the subsequent evolution of the call component (the chuck) that stimulates it. This supports the sensory exploitation idea, which posits that signals evolve to match preexisting features of receiver systems.
Brain Structures of a Medaka Mutant, el(eyeless), in Which Eye Vesicles Do Not Evaginate
Authors: Ishikawa Yuji , Yoshimoto Masami , Yamamoto Naoyuki , Ito Hironobu , Yasuda Takako , Tokunaga Fumio , Iigo Masayuki , Wakamatsu Yuko , Ozato Kenjiro
Published: April 2003

Eye development and brain structures of a mutant teleost fish were investigated. The el(eyeless) mutation in medaka (Oryzias latipes) is recessive and affects eye formation; in the most severe cases, it results in the absence of eyes. Developmental studies revealed that normal eyeballs are not formed in the el mutant embryos, but small optic cup-like structures differentiate in situ in the walls of the prosencephalon without evagination. The anophthalmic el homozygous fish hatched normally, although they did not respond behaviorally to visual stimuli. A small fraction of these fish grew to adulthood. In the adult anophthalmic el homozygous fish, the brain exhibited abnormalities in several subdivisions. A pair of small abnormal protrusions was observed on the surface of the ventral telencephalon and preoptic area. Immunocytochemistry using a rhodopsin monoclonal antibody showed that opsin-positive cells were present in the abnormal structures. Bodian staining showed that the optic nerves were present near the abnormal structures, although the number of optic nerve fibers was extremely small. The optic tectum was extremely small, and the thickness of the stratum opticum and stratum fibrosum et griseum superficiale was reduced. These behavioral and morphological observations suggest that the adult anophthalmic el homozygous fish are functionally blind, although small retina-like structures were partially differentiated and persisted in the adult fish brain. Moreover, the adult anophthalmic el homozygous fish were infertile, and the sizes of the hypophysis and the hypothalamus were reduced. Thus, the el mutation affects not only the brain structures that are related to the visual system but also those related to the reproductive system.
Acute Effects of a Class IA Antiarrhythmic Drug on the Ventricular Evoked Response Amplitude in Patients with Cardiac Pacemakers
Authors: Schuchert Andreas , Meinertz Thomas
Published: April 2003

Some newer cardiac pacemakers are able to control the efficacy of the ventricular pacing pulse beat by beat and to adjust the ventricular output to the actual pacing threshold. This capture verification is based on the detection of the ventricular evoked response amplitude, which has to be detected immediately after the pacing pulse. The sensitivity of the pacemaker to detect the evoked response amplitude must be adjusted individually to avoid the simultaneous detection of lead polarization. The aim of the present study was to evaluate the acute effects of a class IA antiarrhythmic drug on the evoked response amplitude and polarization in 13 pacemaker patients. The implanted pacemaker was the VVIR pacemaker Regency (St. Jude Medical), which provides the automatic capture verification algorithm Autocapture. The patients received 50 mg of ajmaline intravenously within 1 min. The evoked response amplitude and polarization were measured before and 2, 4, 6 and 8 min after ajmaline injection. The evoked response amplitude significantly decreased from 8.0 ± 4.0 mV to a minimum value of 6.4 ± 3.1 mV 2 min after drug administration. The decrease remained significant from the end of the application up to 6 min. The recommended sensitivity setting for the evoked response significantly (p < 0.05) decreased from 4.0 ± 2.3 mV before to 3.1 ± 1.3 mV 2 min after administration. No significant changes were observed for polarization. After the ajmaline application in 2 patients, the pacemaker recommended the deactivation of Autocapture for 9 min in 1 patient and 12 min in the other. The reasons were a decrease in the evoked response amplitude from 3.1 to 1.9 mV and from 9.0 to 5.7 mV, respectively, with a polarization ranging to about 3.0 mV. In conclusion, the ajmaline injection decreased the evoked response amplitude for some minutes. These findings indicate that antiarrhythmic drugs can alter the automatic capture verification function.
Which Lead for Q-T Interval Measurements?
Authors: Davey P.P.
Published: April 2003

There are several Q-T interval measures (individual lead, mean Q-T interval or Q-T dispersion) from a 12-lead ECG. Which should be used? As the ECG provides twelve different measures of the heart’s ‘true’ Q-T interval, and as, ‘a priori’, no one measure is any better or worse than any other measure at estimating the ‘true’ Q-T interval, the best measure is the average of these twelve measures, i.e., the mean Q-T interval. The best single lead to measure the Q-T interval is the lead that relates most closely to the mean Q-T interval which in 49 subjects with cardiac diseases was lead V3, then lead II. The longest lead Q-T interval relates poorly to the mean and to the individual lead Q-T intervals and therefore carried information different to and quite unique from these measures. This unique information is Q-T dispersion which relates well to the longest lead Q-T interval (r = 0.71, p < 0.001).
Technetium-99m Sestamibi/Tetrofosmin Myocardial Perfusion Scanning in Cardiac and Noncardiac Sarcoidosis
Authors: Eguchi Mariko , Tsuchihashi Kazufumi , Hotta Daisuke , Hashimoto Akiyoshi , Sasao Hisataka , Yuda Satoshi , Nakata Tomoaki , Shijubou Noriharu , Abe Shosaku , Shimamoto Kazuaki
Published: April 2003

Left ventricular (LV) and right ventricular (RV) involvement in sarcoidosis must be firmly confirmed to determine patients’ prognosis. We examined whether myocardial perfusion images using technetium-99m single photon emission computed tomography (SPECT) have a diagnostic benefit in the evaluation of biventricular involvement. Sixteen patients with sarcoidosis, aged 21–78 (54 ± 12) years old, 5 males and 11 females, complicated with cardiac disease (cardiac sarcoidosis, n = 6) including tachyarrhythmias of ventricular origin (n = 5), atrioventricular block (n = 4), and congestive heart failure (NYHA ≧ II, n = 1), were enrolled in this study. Myocardial SPECT using technetium-99m sestamibi or tetrofosmin was performed and semiquantitatively scored for comparison with 25 control subjects. Perfusion abnormalities were more frequently recognized in sarcoidosis (LV 5/16, 31% and RV 14/16, 88% vs. LV 0/25, 0% and RV 8/25, 32% in controls). LV involvement had a close correlation with atrioventricular block and with congestive heart failure, and multiple sites of RV involvement correlated with ventricular tachyarrhythmia of RV origin. Total number of defect segments were highest in cardiac sarcoidosis (18/30, 60% vs. 19/60, 32% in noncardiac sarcoidosis, and 11/150, 7% in controls, p = 0.0001), and semiquantitatively evaluated total LV and RV scores (ranging from 0 to 18) were higher than those of controls (15.1 ± 1.8 vs. 11.4 ± 3.0 in noncardiac sarcoidosis, and 9.0 ± 5.0 in cardiac sarcoidosis) and exhibited a significant positive linear correlation with the RV ejection fraction (y = 19.8 + 1.83x, r = 0.786, p = 0.001). Biventricular SPECT using technetium-99m is clinically useful for the noninvasive evaluation of both ventricular involvements in sarcoidosis.
Assessment of Pseudohypertrophy as a Measure of Left-Ventricular Compression in Patients with Cardiac Tamponade
Authors: Feinberg Micha S. , Popescu Bogdan A. , Popescu Andreea C. , Di Segni Elio , Jonas Michael , Rabinowitz Babeth , Kaplinsky Elieser , Schwammenthal Ehud
Published: April 2003

Background: Left-ventricular pseudohypertrophy reflecting left-ventricular compression was reported in a selected group of patients with cardiac tamponade. Hypothesis: Criteria for the presence of pseudohypertrophy can be established to guide its use as a sign of left-ventricular compression in patients with cardiac tamponade. Methods: Left-ventricular wall thickness, diameters, relative diastolic wall thickness (%) = (posterior wall thickness/end diastolic radius) x 100 and estimated left-ventricular mass were measured in patients with small, moderate and large pericardial effusion, in patients with cardiac tamponade before and after pericardiocentesis (16 patients in each group) and in 30 control subjects with normal echocardiograms. Results: Left-ventricular posterior wall thickness was increased (12 ± 2 vs. 9 ± 1 mm, p < 0.001), left-ventricular end-diastolic diameter was reduced (3.9 ± 0.5 vs. 4.6 ± 0.3 cm, p < 0.001) and relative left-ventricular diastolic wall thickness was increased (61 ± 13 vs. 41 ± 4.5%, p < 0.001) only in patients with cardiac tamponade compared to controls, but not in patients with small, moderate and large effusions, respectively (relative wall thickness: 42 ± 5, 41 ± 7 and 44 ± 7%, p = NS). Mean values of the estimated left-ventricular mass were similar in all groups. Following pericardiocentesis all parameters were normal. Conclusions: Despite normal left-ventricular mass, relative left-ventricular diastolic wall thickness is elevated in patients with cardiac tamponade. In contrast it is normal in patients with various degrees of pericardial effusion supporting its use as a quantitative measure of left-ventricular compression in patients with suspected cardiac tamponade.
Biochemical Markers of Ischaemia for the Early Identification of Acute Myocardial Infarction without ST Segment Elevation
Authors: Haastrup Benedikte , Gill Sabine , Kristensen Søren Risom , Jørgensen Poul Jørgen , Glatz Jan F.C. , Haghfelt Torben , Hørder Mogens
Published: April 2003

Blood was collected on admission and after 1–2 h in 130 consecutive patients admitted with typical chest pain in order to assess the capacity of myoglobin, fatty-acid-binding protein (FABP), CK-MB mass, and troponin I (TnI) in the early identification of acute myocardial infarction (AMI) without ST elevation. Using the maximum value within 6 h of onset of symptoms, AMI was detected with a 90–95% sensitivity and a 81–94% specificity by FABP at a cut-off level 8–12 µg/l, or 81–86% and 89–93%, respectively, by myoglobin at a cut-off level 70–90 µg/l. CK-MB mass and TnI had low sensitivity, albeit very high specificity. As almost all AMI patients were identified within 6 h, serial measurements of FABP or myoglobin ruled out AMI with a very high degree of certainty. Due to the low prevalence of AMI (16%), the positive predictive values were modest (47–73%), yet increasing the probability of AMI by a factor 3–4. Myoglobin and FABP are very useful markers in the early triage of chest pain patients.
In vivo Magnetic Resonance Imaging and Surgical Histopathology of Intracardiac Masses: Distinct Features of Subacute Thrombi
Authors: Paydarfar David , Krieger Derk , Dib Nabil , Blair Richard H. , Pastore John O. , Stetz Jr. Joseph J. , Symes James F.
Published: April 2003

We evaluated intracardiac masses in vivo, in situ and histologically to determine tissue properties revealed by magnetic resonance (MR) imaging. In 15 consecutive patients scheduled for cardiotomy, the cardiac chambers were studied preoperatively with MR imaging and echocardiography. Visual examination of one or more chambers was performed during cardiotomy for mitral valve replacement, aneurysmectomy, atrial septal repair and atriotomy. Six thrombi (1 atrial appendage, 5 ventricular) and 2 atrial myxomas were removed and subjected to histological analysis. All masses were detected preoperatively by MR imaging. The smallest was a subacute 3-mm mural clot in the left ventricle and was undetected by transesophageal and transthoracic echocardiography. The 3 subacute clots had homogeneously low MR signals, did not enhance with gadolinium and exhibited magnetic susceptibility effects; histopathology confirmed these clots to be avascular and laden with dense iron deposition related to hemoglobin breakdown products. The 3 organized clots had intermediate and heterogeneous MR signals and multiple areas of gadolinium enhancement. The 2 myxomas had low MR signals and gadolinium enhancement in the core and septal attachment; these areas had dense neovascular channels. Subacute thrombi appear to have MR features that are distinct from organized thrombi and myxomas, and MR images of subacute thrombi contrast sharply with normal cardiac structures, enabling detection of thin mural clots that may be echographically occult. These findings may be of value, because a subacute clot may be more likely than an organized thrombus to give rise to an embolus.
Interrogation of the Tricuspid Annulus by Doppler Tissue Imaging in Patients with Chronic Pulmonary Hypertension: Implications for the Assessment of Right-Ventricular Systolic and Diastolic Function
Authors: Moustapha Ali , Lim Marcy , Saikia Sangeeta , Kaushik Vinod , Kang Seung-Ho , Barasch Eddy
Published: April 2003

Background: Chronic pulmonary hypertension (CPHT) has a great impact on both right-ventricular (RV) systolic and diastolic properties and the assessment of those properties is not always feasible by traditional echocardiographic examination. Doppler tissue imaging (DTI) interrogation of the tricuspid annulus (TA) identifies the pattern of TA motion (TAM) and can help to assess RV function when other methods are not feasible. Aims: To determine RV systolic and diastolic function in patients with CPHT using DTI parameters of the TA. Methods: Eighty-seven patients with CPHT and 90 normal controls were studied. DTI parameters were measured including early diastolic, late diastolic and systolic velocities and time velocity integrals (TVI) of the TAM at both its lateral and medial aspect. Results: Early diastolic and systolic velocities, the ratio of early to late diastolic velocities and TVI of TAM at both lateral and medial aspects were significantly decreased in patients with CPHT compared to controls. No significant differences were seen in late diastolic velocities and TVI in both groups. Systolic velocity of the TAM at both its lateral and medial aspects significantly correlated with RV systolic function as measured by fractional RV area change. Conclusions: DTI of the TAM can be used to assess RV systolic and diastolic properties in patients with CPHT.
Comparison of Adenosine and Exercise Stress Test for Quantitative Perfusion Imaging in Patients on Beta-Blocker Therapy
Authors: Müller-Suur Roland , Eriksson Sven V. , Strandberg Lars Erik , Mesko Laszlo
Published: April 2003

Beta-blocker therapy is used to decrease myocardial ischemia during exercise but may cause suboptimal diagnostic performance in exercise stress testing. The aim of the present study was to compare results of quantitative technetium-99-sestamibi single photon emission tomography (SPECT), following exercise stress test or pharmacological stress test with adenosine. We chose adenosine as comparison, since betablockers may not interfere with adenosine induced vasodilatation and therefore possibly may not interfere with its diagnostic performance. Sixteen patients with angiographically documented coronary disease (5 single-vessel, 6 two-vessel and 5 three-vessel disease), who were chronically treated with beta-blockers, performed SPECT imaging at rest, following bicycle exercise and following adenosine infusion in random order. The SPECT data were analyzed visually and quantitatively, using dedicated computer software (CEqual). According to both visual and quantitative SPECT analysis, adenosine was superior to show reversibility. Higher reversibility extent (50 ± 15 vs. 26 ± 12 pixels, p < 0.01) and more intense reversibility severity (110 ± 29 vs. 49 ± 23 sum of SDs, p < 0.05) were observed during adenosine than exercise. Conclusions: Less myocardial perfusion abnormalities during exercise than during adenosine stress in patients treated with beta-blockers may indicate less ischemia but also an impaired diagnostic performance. Thus adenosine stress test should be preferred to optimize the diagnostic sensitivity in patients during beta-blocker treatment.
Coronary Artery Calcium Determined by Electron Beam Computed Tomography for Predicting Angiographic Coronary Artery Disease in Moderate- to High-Risk Chinese Patients
Authors: Chen Lung-Ching , Ding Philip Yu-An , Chen Jaw-Wen , Wu Mei-Han , Liu Ju-Chi , Lan Gong-Yau , Chern Ming-Sheng , Chang Cheng-Yen , Chang Mau-Song
Published: April 2003

The aim of this study was to evaluate the prevalence of coronary calcification among moderate- to high-risk Chinese patients and to evaluate the ability of the coronary calcium score determined by electron beam computed tomography (EBCT) to predict angiographic coronary artery disease in this population. We enrolled 163 consecutive patients and analyzed their cardiovascular risk factors, coronary calcium scores and coronary angiogram results. One hundred and twenty-five patients (76.7%) had a positive EBCT scan result (coronary calcium score >0). The prevalence of calcification and the calcium scores showed a graded relation to the number of cardiovascular risk factors and age (p < 0.001 for trend). Coronary calcium scores showed statistically significant differences between patients with angiographic evidence of coronary artery disease and patients with normal coronary angiography (p < 0.05), but could not differentiate between patients with significant and insignificant coronary artery disease. Receiver operating characteristic curve analysis showed that a coronary calcium score >5 predicted angiographic coronary artery disease with 93% sensitivity and 86% specificity (area under the curve 0.95 ± 0.019). Multivariate analysis showed a coronary calcium score >5 to be the strongest independent predictor of angiographic coronary artery disease (odds ratio 120.7, 95% confidence interval 21.7–671.4; p < 0.001). Coronary calcium score determined by EBCT appears to have a similar predictive value in Chinese patients as it does in other ethnic populations that have been reported to date.
Prognostic Implications of Left Ventricular Diastolic Dysfunction with Preserved Systolic Function following Acute Myocardial Infarction
Authors: Poulsen Steen H. , Møller Jacob E. , Nørager Betina , Egstrup Kenneth
Published: April 2003

The contribution of diastolic dysfunction in patients with preserved left ventricular (LV) systolic function to impaired functional status and cardiac mortality in myocardial infarction (MI) is unknown. In the present study, assessment of LV diastolic function was performed by Doppler analysis of the mitral and pulmonary venous flow, and the propagation velocity of early mitral flow by color M-mode Doppler echocardiography in 183 consecutive patients at day 5–7 following their first acute MI. Patients were classified into four groups: group A: preserved LV systolic and diastolic function (n = 73); group B: LV systolic dysfunction with preserved diastolic function (n = 10); group C: LV diastolic dysfunction with preserved systolic function (n = 60); group D: combined LV systolic and diastolic dysfunction (n = 40). The cardiac mortality rate at 1 year was significantly higher in groups C (13%) and D (38%) compared to A (2%) (p < 0.01). Multivariate regression analysis identified LV diastolic dysfunction (p = 0.001), Killip class ≧II (p = 0.006), and age (0.008) as predictors of cardiac death or readmission due to heart failure. The presence of LV diastolic dysfunction with preserved systolic dysfunction is associated with increased morbidity and mortality following acute MI.
Myocardial Ultrasonic Tissue Characterization for Estimating Histological Abnormalities in Hypertrophic Cardiomyopathy: Comparison with Endomyocardial Biopsy Findings
Authors: Mizuno Reiko , Fujimoto Shinichi , Yamaji Kunihiro , Yutani Chikao , Hashimoto Toshio , Nakamura Shinobu
Published: April 2003

Aims: In this study, we investigated the clinical usefulness of ultrasonic tissue characterization with integrated backscatter for the evaluation of myocardial histological abnormalities in comparison with endomyocardial biopsy findings in patients with hypertrophic cardiomyopathy. Methods: Twenty patients with hypertrophic cardiomyopathy and 20 normal subjects were enrolled in this study. We measured two parameters for the ultrasonic tissue characterization with integrated backscatter: the magnitude of the cardiac-cycle-dependent variation in integrated backscatter signals (cdv-IB) and the mean value of integrated backscatter signals calibrated by the pericardium (cal-IB). These parameters were measured at both the interventricular septum and the left ventricular posterior wall. Histological findings of right ventricular endomyocardial biopsy specimens were analyzed by computer image analyzer. Results: cdv-IB was significantly lower and cal-IB significantly higher in both the interventricular septum and the left ventricular posterior wall in patients with hypertrophic cardiomyopathy compared with normal subjects. In patients with hypertrophic cardiomyopathy, the degree of myocardial disarray, interstitial fibrosis, and nonhomogeneity of myocyte size showed positive correlations with cal-IB and negative correlations with cdv-IB. Conclusions: Ultrasonic tissue characterization with IB enables the noninvasive evaluation of myocardial histological abnormalities in patients with hypertrophic cardiomyopathy.
A Double-Blind, Parallel-Group Study of Amlodipine versus Long-Acting Nitrate in the Management of Elderly Patients with Stable Angina
Authors: Hall Roger , Chong Camilla
Published: April 2003

Ninety-seven elderly patients with stable angina were included in a 28-week, randomized, double-blind, parallel-group comparison of amlodipine 5–10 mg and isosorbide mononitrate 25–50 mg once daily. The total exercise time, as limited by angina, was recorded together with the median incidence per week of angina attacks and glyceryl trinitrate consumption. Safety was assessed by adverse event frequency, measurement of vital signs and laboratory parameters, and quality of life. At the final visit, the total exercise time was significantly greater relative to baseline with amlodipine than isosorbide mononitrate (final/baseline difference: 112.2 vs. 32.2, p = 0.016). There were no statistically significant differences between the groups in relation to the incidence of adverse events. Once daily amlodipine provides significantly better control of stable angina than isosorbide mononitrate in this elderly population.
Sustained Benefit from Ultrafiltration in Moderate Congestive Heart Failure
Authors: Agostoni PierGiuseppe , Marenzi GianCarlo
Published: April 2003

Body fluids, particularly in the thorax, are increased in moderate congestive heart failure, even if diuretic treatment is appropriate. Ultrafiltration, differently from diuretics, removes isotonic fluid and therefore the greatest possible amount of sodium per unit of fluid withdrawn, providing a physiologic dehydration. This results in improvement in the patient’s clinical condition, exercise capacity, lung function, as shown by improvement of standard pulmonary function tests, lung mechanics during exercise, and norepinephrine kinetics during exercise and orthostatic tilting.
A Novel Approach to the Treatment of Chronic Fluid Overload with a New Plasma Separation Device
Authors: Ronco Claudio , Ricci Zaccaria , Bellomo Rinaldo , Bedogni Francesco , Handley Hal , Gorsuch Rey , Levin Nathan
Published: April 2003

Many patients with congestive heart failure suffer at some point in their therapy from severe fluid overload, and a significant proportion of patients become unresponsive to diuretic drug therapy. In this paper, we propose a new experimental approach to plasma purification and the treatment of severe fluid overload in acute care patients. Plasma can be extracted directly from the patient through an intracorporeal catheter temporarily placed within the inferior vena cava. Plasma separation is accomplished through a proprietary membrane placed on the tip of the catheter. A simple circuit performs plasma removal. The extracted plasma is then available for any type of treatment before being returned to the patient via a second lumen in the same catheter. Plasma flow rates between 3 and 8 ml/min have been achieved and animal tests led to the removal of more than 2,000 ml of plasma water in 24 h. The current varieties of blood purification or ultrafiltration techniques employ extracorporeal extraction of blood from the patient in order to perform treatment. Removal of the cellular component in the extracorporeal fluid circuit may reduce the current problems associated with extracorporeal circuits, such as cellular lysis and viscosity-related problems. Plasma treatment is already successfully performed in a variety of therapies, including renal replacement therapies and plasmapheresis. The therapy proposed here may extend the utility of plasma treatment to the acute cardiology patient. The system could become an important complementary therapy for patients with congestive heart failure for whom classic methods of treatment have failed or simply are not available.
Fluoride Deposition in the Aged Human Pineal Gland
Authors: Luke J.
Published: April 2003

The purpose was to discover whether fluoride (F) accumulates in the aged human pineal gland. The aims were to determine (a) F–concentrations of the pineal gland (wet), corresponding muscle (wet) and bone (ash); (b) calcium–concentration of the pineal. Pineal, muscle and bone were dissected from 11 aged cadavers and assayed for F using the HMDS–facilitated diffusion, F–ion–specific electrode method. Pineal calcium was determined using atomic absorption spectroscopy. Pineal and muscle contained 297±257 and 0.5±0.4 mg F/kg wet weight, respectively; bone contained 2,037±1,095 mg F/kg ash weight. The pineal contained 16,000±11,070 mg Ca/kg wet weight. There was a positive correlation between pineal F and pineal Ca (r = 0.73, p<0.02) but no correlation between pineal F and bone F. By old age, the pineal gland has readily accumulated F and its F/Ca ratio is higher than bone.
Comparison of Erythritol and Xylitol Saliva Stimulants in the Control of Dental Plaque and Mutans Streptococci
Authors: Mäkinen K.K. , Isotupa K.P. , Kivilompolo T. , Mäkinen P.L. , Toivanen J. , Söderling E.
Published: April 2003

The effect of 2–month usage of saliva–stimulating pastils containing either erythritol or xylitol was studied in a cohort of 30 subjects assigned to the respective polyol groups (n = 15). The daily consumption level of both polyols was 5.2 g, used in 5 daily chewing episodes. The mean weight of total plaque mass (collectable during a standard period of 3 min from all available tooth surfaces) was reduced significantly in the xylitol–group, while no such effect was observed in the erythritol–group. This reduction in plaque mass was accompanied by a significant reduction in the turbidity readings (A660) of aqueous plaque suspensions; no such effect was observed in the erythritol–group. However, plaque protein levels did not differ between baseline and endpoint in either polyol group. The plaque and salivary levels of Streptococcus mutans and plaque levels of total streptococci were reduced significantly in the xylitol–group, while no such effect was detected in the erythritol–group. However, either polyol regimen had no effect on plaque levels of S. sobrinus. The results suggest that systematic use of xylitol–containing saliva stimulants may be more effective in controlling some oral–hygiene–related and caries–associated parameters than similar use of erythritol–containing products. The results also speak for a special relationship between xylitol and S. mutans. However, owing to the great potential of erythritol as a caries–reducing agent – based on the tetritol nature of erythritol – the present laboratory results should be considered preliminary and subject to verifying clinical studies.