bluuebunny/crossref_metadata_2025 huggingface dataset:
Ca2+-Induced Inhibition of Adenylyl Cyclase in Turkey Erythrocyte Membranes
Authors: Demirel Emine , Ugur Özlem , Onaran H. Ongun
Published: April 2003

We investigated the effects of calcium ions (Ca2+) on the adenylyl cyclase activity in purified turkey erythrocyte membranes. Results showed the following: (i) Ca2+ inhibits cAMP accumulation stimulated by isoproterenol (1 µmol/l), NaF + AlCl3 (10 mmol/l + 20 µmol/l) or forskolin (10 µmol/l) in EGTA-washed turkey erythrocyte membranes. IC50 of free [Ca2+] is approximately 0.1 mmol/l in the presence of Mg2+ (2.5 mmol/l) and isobutylmethylxanthine (1 mmol/l). (ii) The potency of Ca2+ to inhibit cAMP accumulation is independent of the type of stimulus used to activate the adenylyl cyclase. We also evaluated the calcium sensitivity of the basal cAMP accumulation in the presence of GTP (10 µmol/l) and Mg2+ (2.5 mmol/l) which was also inhibited by Ca2+ with the same potency. (iii) The inhibition pattern of cAMP accumulation is not affected by the presence of added calmodulin (100 nmol/l). (iv) Ca2+ is ineffective on the binding of isoproterenol to the β-adrenoceptors. (v) Increasing the concentration of Ca2+ does not induce an observable activation of cyclic nucleotide phosphodiesterase in the present experimental conditions. Thus, we concluded that the inhibition of cAMP accumulation is due to an inhibition of the adenylyl cyclase rather than the activation of phosphodiesterase(s). The presence of a yet unidentified isoform of adenylyl cyclase that can be directly inhibited by Ca2+ or a Gi protein that can be activated by Ca2+ seems to explain these results. In either case, these results provide an additional mode of cross-talk that can take place between the Ca2+- and cAMP-signaling systems.
Anticonvulsant Properties of 1,4-Benzodiazepine Derivatives in Amygdaloid-Kindled Seizures and Their Chemical Structure-Related Anticonvulsant Action
Authors: Fukinaga Masafumi , Ishizawa Keisuke , Kamei Chiaki
Published: April 2003

The effects of 14 different 1,4-benzodiazepines on amygdaloid-kindled seizures and their chemical structure-related anticonvulsive actions were studied. The prophylactic effects of 1,4-benzodiazepines on amygdaloid-kindled seizures were also examined. Male Wistar strain rats were used in this study. Rats were anesthetized with pentobarbital sodium (35 mg/kg i.p.) and bipolar electrodes were implanted into the right amygdala. The stimulating parameters were 1 ms pulse duration, 60 Hz frequency and a 1 s duration at an intensity just sufficient to induce afterdischarge (AD). All the 1,4-benzodiazepines depressed both seizure stage and AD duration of amygdaloid-kindled seizures. Of the 1,4-benzodiazepines, prazepam, flutoprazepam and flurazepam with a long alkyl chain at position 1 were less effective than the drugs having a hydrogen or methyl group at the same position. Nitrazepam, nimetazepam, flunitrazepam and clonazepam which have a nitro group at position 7 showed more potent antiepileptic activity than the drugs with a chloro group. Certain 1,4-benzodiazepines caused inhibition of the development of amygdaloid-kindled seizures. The existence of a hydrogen or methyl group at position 1 and a nitro group at position 7 is important for exhibiting potent anticonvulsant activity in amygdaloid-kindled seizures. Introduction of an oxygen group at position 2 is also necessary for high activity. 1,4-benzodiazepines had not only therapeutic but also prophylactic effects on amygdaloid-kindled seizures.
Pharmacological Characteristics of MJ-451, a New Benzopyran- Derived ATP-Sensitive Potassium Channel Opener, in Guinea Pig Isolated Trachea
Authors: Lin Chien-Huang , Lee Yen-Mei , Sheu Joen-Rong , Cheng Chen-Yu , Chang Ming-Jyh , Yen Mao-Hsiung
Published: April 2003

In this study, we determined the pharmacological activities of MJ-451 (6-cyano-3S,4R-dihydro-2,2-dimethyl-2H-3-hydroxy-4-[2-oxo-5S-1-hydroxmethyl)-1-pyrrolidinyl]-1-benzopyran) in guinea pig isolated trachea and compared its effects with those of cromakalim. MJ-451 (0.1–10 µmol/l) and cromakalim (0.01–1 µmol/l) produced concentration-dependent relaxation of guinea pig isolated trachea precontracted with carbachol (0.5 µmol/l) or histamine (1 µmol/l). MJ-451 (0.03–30 µmol/l), as well as cromakalim (0.03–30 µmol/l), caused a complete and concentration-dependent relaxation of guinea pig isolated trachea precontracted with 20 mmol/l KCl, but did not inhibit the spasmogenic effect of 80 mmol/l KCl. However, theophylline (30–3,000 µmol/l) caused a complete and concentration-dependent relaxation of guinea pig isolated trachea precontracted with either 20 or 80 mmol/l KCl. Propranolol (0.1 µmol/l) markedly antagonized the relaxant action of isoprenaline, but not that of MJ-451 in carbachol-contracted isolated trachea. 8-(p)-sulfophenyltheophylline (150 µmol/l), a selective P1 purinoceptor antagonist, had no effect against the tracheal relaxation induced by MJ-451, but markedly depressed the concentration-response curve of 5′-N-ethylcarboxamidoadenosine. Charybdotoxin (10 µmol/l), a large-conductance Ca2+-activated K+ channel blocker, failed to modify the relaxant activity of MJ-451 in carbachol-contracted isolated trachea. The ATP-sensitive K+ channel blocker, glibenclamide (0.1, 1 and 10 µmol/l) concentration-dependently antagonized the relaxant activity of MJ-451 in carbachol-contracted isolated trachea. It is concluded that MJ-451 is a selective ATP-sensitive K+ channel opener in the tracheal smooth muscle of the guinea pig.
Biphasic Relaxant Response of Ovine Trachealis Muscle to Electrical Field Stimulation: Influence of Cooling
Authors: Mustafa S.M.D. , Oriowo M.A. , Pilcher C.W.T. , Williams K.I.
Published: April 2003

Electrical field stimulation of ovine trachealis muscle produced neurogenic atropine-sensitive contractions under resting conditions. However, when the tissues were precontracted with 5-hydroxytryptamine in the presence of atropine, electrical field stimulation induced a frequency-dependent tetrodotoxin-sensitive relaxation. The relaxation was biphasic, consisting of fast and slow phases. The fast component was attenuated by propranolol, indicating an action on β-adrenoceptors. The slow phase was attenuated by capsaicin and, therefore, involved release of a peptide. These results showed that excitatory responses in ovine trachealis muscles are cholinergically mediated, while both adrenergic and peptidergic components mediate electrically induced relaxation in the trachea. We also examined the influence of lowering bath temperature to 20°C on electrically evoked responses. These were significantly reduced by cooling. At 20°C, under resting conditions, the time-to-peak tension was lengthened, and the amplitude of the contractile responses was significantly (p < 0.05) reduced. In the same preparation, carbachol-induced contractions were not reduced by cooling, indicating that the reduction in electrically induced contractions was probably due to a reduction in transmitter release. Cooling also abolished the fast inhibitory phase (adrenergic in nature) without significantly inhibiting the slow (non-adrenergic, non-cholinergic) component. Propranolol (1 µmol/l) and capsaicin (100 µmol/l) did not affect significantly the slow relaxation observed during cooling. It was concluded that cooling inhibited cholinergically mediated, electrically induced contractions and selectively abolished the adrenergic component of electrically induced relaxant responses.
Prostaglandin E2 in Human Placenta: Its Vascular Effects and Activation of Prostaglandin E2 Formation by Nicotine and Cotinine
Authors: Sastry B.V. Rama , Hemontolor M.E. , Olenick Molly
Published: April 2003

Tobacco smoking by pregnant women increases the frequency of spontaneous abortions and preterm births. Human labor is associated with enhanced intrauterine phospholipid metabolism and production of prostaglandin E2 (PGE2) which induces labor, initiates uterine contractions and maintains the homeostasis of placental blood flow. Therefore, we studied: (a) the influence of nicotine and cotinine on the effects of PGE2 on placental vasculature in perfused human placental cotyledon, and (b) the activation of placental phospholipase A2 (PLA2) by nicotine and cotinine using 1-palmitoyl-2-[1-14C]arachidonyl-phosphatidylethanolamine (PE, 2.2 nmol) as substrate. These studies revealed that: (1) increasing concentrations of PGE2 (10– 150 ng/ml) increased umbilical perfusion pressure by 170 ± 10% (n = 6) of control (100%). Cotinine (2 µg/ml) enhanced this effect at all concentrations of PGE2. Nicotine (2 µg/ml) prevented the effect of PGE2; (2) both cotinine (EC50 470–500 fmol/l) and nicotine (EC50 18–32 pmol/l) activated PLA2 in human placental tissues. These observations indicated that cotinine was more potent than in nicotine activating PLA2 and potentiating the vasoconstrictive effects of PGE2 on fetal placental circulation. Nicotine activates nicotinic receptors and releases placental acetylcholine, a vasodilator of placental arteries. Acetylcholine stimulates muscarinic receptors of endothelial cells resulting in the release of endothelium-derived relaxing factor (EDRF), and possibly nitric oxide. Therefore, nicotine prevents or abolishes the vasoconstrictive effects of PGE2 through the release of EDRF. Cotinine is inactive at nicotinic and muscarinic receptors. Therefore, accumulation of cotinine, the major metabolite of nicotine, in fetal circulation may contribute to production of PGE2 and induction of preterm labor and spontaneous abortions.
Captopril Inhibits Peptidylglycine- α-Hydroxylating Monooxygenase: Implications for Therapeutic Effects
Authors: Mueller S.Alyssa , Driscoll WilliamJ. , Mueller GregoryP.
Published: April 2003

The therapeutic actions of captopril are facilitated by its sulfhydryl moiety which interacts with the metal (Zn2+) prosthetic groups of angiotensin-converting enzyme (ACE; EC 3.4.15.1). This study focused on captopril as an inhibitor of another metal-dependent (Cu2+) enzyme, peptidylglycine-α-hydroxylating monooxygenase (PHM; EC 1.14.17.3). PHM is rate limiting in α-amidation, a COOH-terminal modification that bioactivates several pressor peptides. Captopril inhibited PHM in vitro in a dose-dependent manner with an IC50 of approximately 100 μmol/l. This inhibition was partially reversed by increased concentrations of Cu2+. Structurally similar nonsulfhydryl ACE inhibitors did not affect the activity of PHM. The present findings indicate that the therapeutic effectiveness of captopril may result from actions on a range of metalloenzymes including ACE and PHM.
Effects of Ambroxol on Spontaneous or Stimulated Generation of Reactive Oxygen Species by Bronchoalveolar Lavage Cells Harvested from Patients With or Without Chronic Obstructive Pulmonary Diseases
Authors: Teramoto Shinji , Suzuki Masashi , Ohga Eijiro , Ishii Takeo , Matsui Hirotoshi , Matsuse Takeshi , Ouchi Yasuyoshi
Published: April 2003

We examined the effects of ambroxol on spontaneous or stimulated generation of reactive oxygen species (ROS) by bronchoalveolar lavage (BAL) cells prepared from 6 patients with chronic obstructive pulmonary disease (COPD) and age-matched control subjects without COPD. The ROS produced by BAL cells were measured by the lucigenin-dependent chemiluminescence method. The application of ambroxol into culture media containing BAL cells inhibited spontaneous and stimulated generation of ROS by BAL cells harvested from COPD patients and control subjects in an ambroxol concentration-dependent manner. These results indicate that ambroxol may be a candidate agent for reducing oxidant stresses of airways in COPD.
Intestinal Motor Depression by 7-Nitroindazole through an Action Unrelated to Nitric Oxide Synthase Inhibition
Authors: Heinemann Ákos , Holzer Peter
Published: April 2003

Nitric oxide (NO) is a cotransmitter of inhibitory motor neurons of the enteric nervous system. This study examined the effect of 7-nitroindazole (7-NI), an inhibitor of neuronal NO synthase (NOS), on intestinal peristalsis and muscle activity and compared 7-NI with NG-nitro-L-arginine methyl ester (L-NAME), a nonselective inhibitor of NOS isoforms. Peristalsis in isolated segments of the guinea pig small intestine was triggered by a perfusion-induced rise of the intraluminal pressure. While L-NAME (10–300 μmol/l) lowered the peristaltic pressure threshold (PPT) at which propulsive muscle contractions were elicited, 7-NI (10–300 μmol/l) caused a concentration-related increase in PPT. L-Arginine (1–3 mmol/l) failed to reverse peristaltic motor depression evoked by 7-NI but annulled the L-NAME-evoked stimulation of peristalsis. Drugs which stimulated peristalsis, such as L-NAME, naloxone, apamin and suramin plus pyridoxal phosphate-6-azophenyl-2′-4′-disulphonic acid counteracted the inhibitory effect of submaximally effective concentrations of 7-NI on peristalsis. 7-NI (100–300 μmol/l) inhibited circular muscle contractions evoked by cholecystokinin octapeptide, the NK1 receptor agonist GR-73,632 and indomethacin whereas L-NAME (100–300 μmol/l) failed to inhibit any drug-evoked contraction. These data show that 7-NI, unlike L-NAME, inhibits circular muscle contractions of the gut and depresses intestinal peristalsis. It is concluded that the inhibitory motor action of 7-NI is unrelated to inhibition of neuronal NOS and arises from depression of smooth muscle activity.
Structural Variants of a Human 5-HT1a Receptor Intracellular Loop 3 Peptide
Authors: Ortiz Thomas C. , Devereaux Jr. Marvin  C. , Parker Keith K.
Published: April 2003

To better understand cytoplasmic loop 3/G protein coupling, variations in a bioactive synthetic peptide probe (P1) were constructed according to the published sequences of the human 5HT1a receptor. These probes were tested in a model system of human 5HT1a receptor stably expressed in Chinese hamster ovary cells. In agonist inhibition studies, peptides with amino acid substitutions of residues 6–9 from the amino terminus of loop 3 were less active than P1. Truncated peptide P4, conserving the residue 6–9 region, was also less active than P1. Truncates P5 and P6, deleting the residue 6–9 region, were inactive. When cAMP levels were measured, both substituted peptides were more active than P1 in this negatively coupled system. In contrast, the truncated peptides were without activity in the cAMP assays. Thus, P1 and its derivatives (P2–P6) constitute a small group of peptides with differential uncoupling (agonist inhibition) and signal transduction (cAMP) activities in this G-protein-linked system. It is proposed that these peptides will be useful in future studies detailing the molecular determinants at the receptor/G protein interface.
Inhibition of T-Type and L-Type Ca2+ Currents by Aranidipine, a Novel Dihydropyridine Ca2+ Antagonist
Authors: Masumiya Haruko , Tanaka Yoshio , Tanaka Hikaru , Shigenobu Koki
Published: April 2003

The effects of aranidipine, a novel dihydropyridine Ca2+ channel antagonist, on membrane currents in guinea pig ventricular myocytes and on action potentials in rabbit sinoatrial node tissue were examined. In myocytes, aranidipine (10 nmol/l to 1 μmol/l) concentration-dependently decreased T-type and L-type Ca2+ currents. Aranidipine (1 μmol/l) had little effect on K+ currents. In the sinoatrial node, 0.1 μmol/l aranidipine increased cycle length, and decreased +v̇max and the slope of the phase 4 depolarization. Thus, inhibition of both T-type and L-type Ca2+ currents by aranidipine may partly explain its potent negative chronotropic activity.
Do Airstream Mechanisms Influence Tongue Movement Paths?
Authors: Hoole Philip
Published: April 2003

Velar consonants often show an elliptical pattern of tongue movement in symmetrical vowel contexts, but the forces responsible for this remain unclear. We here consider the role of overpressure (increased intraoral air pressure) behind the constriction by examining how movement patterns are modified when speakers change from an egressive to ingressive airstream. Tongue movement and respiratory data were obtained from 3 speakers. The two airstream conditions were additionally combined with two levels of speech volume. The results showed consistent reductions in forward tongue movement during consonant closure in the ingressive conditions. Thus, overpressure behind the constriction may partly determine preferred movement patterns, but it cannot be the only influence since forward movement during closure is usually reduced but not eliminated in ingressive speech.
Relationship between Rhythmic Behavior and Canonical Babbling in Infant Vocal Development
Authors: Ejiri Keiko
Published: April 2003

The onset of canonical babbling (CB) is a landmark event in infants’ vocal development for spoken language. Previous research has suggested that the onset of CB coincides with the peak period of rhythmic activities. To examine this phenomenon in detail, 28 Japanese infants (14 girls, 14 boys) were observed longitudinally from the age of 5 to 9 months. In the experimental sessions, an audible or an inaudible rattle was placed into a hand of each tested infant. Then the number of times that the infant shook the rattle was counted. In the observational sessions, infants’ spontaneous rhythmic activities under natural conditions were observed. The result shows that rhythmic activities reached their peak around the onset of CB. When the infants began to babble, they shook whichever rattle was in their hand, regardless of its audibility. After this period, they shook the audible rattles more frequently than the inaudible ones. These findings suggest that, around the onset of CB, infants learn to control their motor activities based on auditory feedback.
Investigating Unscripted Speech: Implications for Phonetics and Phonology
Authors: Kohler K.J.
Published: April 2003

This paper looks at patterns of reduction and elaboration in speech production, taking the phenomenon of plosive-related glottalization in German spontaneous speech, on the basis of the ‘Kiel Corpus’, as its point of departure, and proposes general principles of human speech to explain them. This is followed by an enquiry into the nature of a production-perception link, based on complementary data from perceptual experiments. A hypothesis is put forward as to how listeners cope with the enormous phonetic variability of spoken language and how this ability may be acquired. Finally, the need for a new paradigm of phonetic analysis and phonological systematization is stressed, as a prerequisite to dealing adequately and in an insightful way with the production and perception of spontaneous speech.
Language Acquisition as Complex Category Formation
Authors: Lotto Andrew J.
Published: April 2003

Purported units of speech, e.g. phonemes or features, are essentially categories. The assignment of phonemic (or phonetic) identity is a process of categorization: potentially discriminable speech sounds are treated in an equivalent manner. Unfortunately the extensive literature on human categorization has typically focused on simple visual categories that are defined by the presence or absence of discrete features. Speech categories are much more complex. They are often defined by continuous values across a variety of imperfectly valid features. In this paper, several kinds of categories are distinguished and studies using human subjects, animal subjects and computational models are presented that endeavor to describe the structure and development of the sort of complex categories underlying speech perception.
Dynamic Simulation of Human Movement Using Large-Scale Models of the Body
Authors: Pandy Marcus G. , Anderson Frank C.
Published: April 2003

A three-dimensional model of the body was used to simulate two different motor tasks: vertical jumping and normal walking on level ground. The pattern of muscle excitations, body motions, and ground-reaction forces for each task were calculated using dynamic optimization theory. For jumping, the performance criterion was to maximize the height reached by the center of mass of the body; for walking, the measure of performance was metabolic energy consumed per meter walked. Quantitative comparisons of the simulation results with experimental data obtained from people indicate that the model reproduces the salient features of maximum-height jumping and normal walking on the level. Analyses of the model solutions will allow detailed explanations to be given about the actions of specific muscles during each of these tasks.
An Embodiment Perspective on the Acquisition of Speech Perception
Authors: Davis Barbara L. , MacNeilage Peter F.
Published: April 2003

Understanding the potential relationships between perception and production is crucial to explanation of the nature of early speech acquisition. The ‘embodiment’ perspective suggests that mental activity in general cannot be understood outside of the context of body activities. Indeed, universal motor factors seem to be more responsible for the distribution of early production preferences regarding consonant place and manner, and use of the vowel space than the often considerable cross-language differences in input available to the perceptual system. However, there is evidence for a perceptual basis to the establishment of a language-appropriate balance of oral-to-nasal output by the beginning of babbling, illustrating the necessary contribution of ‘extrinsic’ perceptual information to acquisition. In terms of representations, at least one assumption that segmental units underlying either perception or production in early phases of acquisition may be inappropriate. Our work on production has shown that the dominant early organizational structure is a relatively unitary open-close ‘frame’ produced by mandibular oscillation. Consideration of the role of ‘intrinsic’ (self-produced) perceptual information suggests that this frame may be an important basis for perceptual as well as production organization.
Familial Occurrence of an Arteriovenous Fistula with a Giant Perimedullary Pseudoaneurysm of the Thoracic Spinal Cord in 2 Young Siblings
Authors: Khoo Larry T. , Teitelbaum George P. , Stanley Philip , Hieshima Grant , Levy Michael L. , McComb J. Gordon
Published: April 2003

Two siblings, a sister at age 3 years and a brother (15 years later) at 4 years of age, both presented with similar clinical pictures consisting of back pain, progressive gait difficulty, lower extremity weakness and hyperreflexia. Imaging studies in both cases showed the presence of a perimedullary mass with expansion of the bony spinal canal at T10–T12. Angiography demonstrated almost identical vascular lesions that in each case was being fed by a single left-sided T8 fistulous vessel that expanded into a giant perimedullary venous pseudoaneurysm. Each malformation was successfully obliterated using endovascular techniques, balloon occlusion of the feeding vessel in the first case and coil embolization of the pseudoaneurysm in the second. Following treatment the neurologic deficits resolved in both patients. These young siblings represent the first known case of familial occurrence of very similar giant perimedullary venous pseudoaneurysms of the thoracic spinal cord.
Percutaneous Placement of Ventriculoatrial Shunts in the Pediatric Population
Authors: Britz Gavin W. , Avellino Anthony M. , Schaller Robert , Loeser John D.
Published: April 2003

The percutaneous placement of ventriculoatrial (VA) shunts has been previously described, usually in adults. We report a series of 7 pediatric cases ranging from 6 to 17 years. Five patients were female and 2 were male. All patients had prior ventriculoperitoneal (VP) shunts for hydrocephalus, of which 1 had been subsequently converted to a ventriculopleural shunt. Indications for conversion to a VA shunt were intra-abdominal infection in 6 cases and chronic pleuritic chest pain in 1 patient. The venous entry was the subclavian vein in all cases. All patients have remained asymptomatic since the operation. There were no complications associated with the procedures, with follow-up ranging from 2 to 12 months. This technique is a viable alternative to the open cervical approach for venous entry to the right atrium in the pediatric population.
Symptomatic Moyamoya Disease and Aortic Coarctation in a Patient with Noonan’s Syndrome: Strategies for Management
Authors: Schuster James M. , Roberts Theodore S.
Published: April 2003

Noonan’s syndrome is a multiple congenital anomaly syndrome with characteristic facial features, short stature, congenital heart defects and a recently reported association with moyamoya disease. We report a case of symptomatic moyamoya disease and aortic coarctation in a patient with Noonan’s syndrome. The case illustrates the need for a rational, coordinated treatment plan for dealing with the cardiac and neurologic syndromic anomalies to help avoid undesirable outcomes.
Immediate Posttraumatic Seizures: Is Routine Hospitalization Necessary?
Authors: Dias Mark S. , Carnevale Frank , Li Veetai
Published: April 2003

Objective: A recent Internet survey of pediatric neurosurgeons showed that 86% routinely admitted children with immediate posttraumatic seizures (PTS) for a brief period of observation. We wished to determine whether certain children meeting predefined criteria could instead be safely discharged from the emergency room. Methods: We reviewed the records of children admitted during the past 5 years with a diagnosis of seizure and head injury. Children with a minor head injury, a PTS occurring within 24 h of injury and no intracranial abnormalities on admission CT scan were included. Children with previous neurological conditions, a history of prior seizures (other than PTS or febrile seizures), a prior history of anticonvulsant use, or intracranial abnormalities on the admission CT scan were excluded. Records were abstracted for child’s age, gender, length of admission, previous history of PTS or febrile seizures, mechanism of injury, location of impact, time between impact and PTS, the number, length and type of PTS, Glasgow Coma Score (GCS) on admission, subsequent complications and hospital costs. Results: Seventy-one children met the inclusion criteria. Eleven children presented to the emergency room with prolonged seizures, transient apnea or persistently low GCS and required admission to the intensive care unit (ICU). Among the 60 remaining children with simple PTS, none had further seizures during the follow-up period, and none had significant complications. The average cost of hospitalization was known for 58 children; after excluding the costs for 5 patients who were admitted to the ICU, the average hospital cost amounted to USD 1,615 per patient. Conclusions: Our data suggest that children with isolated minor head injuries and simple PTS who recover fully in the emergency room, whose CT scans show no intracranial abnormalities and who have no prior history of neurological disease, epilepsy or anticonvulsant use are at low risk for recurrent seizures or neurological complications, and could potentially be sent home to a reliable caretaker and a stable home situation. However, because of the limited sample size in this study, the statistical risk of a bad outcome may be as high as 9%; we therefore suggest that much larger studies are potentially needed before this becomes a standard policy.
Effect of Intrauterine Myelomeningocele Repair on Central Nervous System Structure and Function
Authors: Tulipan Noel , Bruner Joseph P. , Hernanz-Schulman Marta , Lowe Lisa H. , Walsh William F. , Nickolaus Delia , Oakes W. Jerry
Published: April 2003

Background: It has been postulated that intrauterine myelomeningocele repair might improve neurologic outcome in patients with myelomeningocele. A total of 59 such procedures have been performed at Vanderbilt University. Preliminary results suggested that the degree of hindbrain herniation is reduced by intrauterine repair. In an attempt to further quantify the possible benefits of this surgery, a subset of these patients was brought back to Vanderbilt for study. Methods: A group of 26 patients who had undergone intrauterine myelomeningocele repair underwent an extensive evaluation which included manual muscle testing, MR imaging and precise determination of the anatomic level of their lesions as well as multiple other tests. The results of this analysis were compared to those in 2 groups of historical controls. Results: In this group of patients intrauterine myelomeningocele repair substantially reduced the incidence of moderate to severe hindbrain herniation (4 vs. 50%). The incidence of shunt-dependent hydrocephalus was more modestly reduced (58 vs. 92%). The average level of leg function closely matched the average anatomic level of the lesion in both the fetal surgery and control groups. Conclusion: The most dramatic effect of intrauterine repair appears to be on hindbrain herniation. A less dramatic, but significant, reduction in shunt-dependent hydrocephalus is also seen. Prospective patients should be cautioned not to expect improvement in leg function as the result of this surgery. The potential benefits of surgery must be carefully weighed against the potential risks of prematurity.
Inflicted Traumatic Brain Injury: Relationship of Developmental Outcome to Severity of Injury
Authors: Ewing-Cobbs Linda , Prasad Mary , Kramer Larry , Landry Susan
Published: April 2003

Inflicted traumatic brain injury (TBI) is a frequent consequence of physical child abuse in infants and children. Twenty-eight children who were 2–42 months of age when hospitalized for moderate to severe TBI were enrolled in a prospective, longitudinal study of neurobehavioral outcome following acquired brain injury. Relative to a comparison group, the children with inflicted TBI had significant deficits in cognitive, motor and behavioral domains when assessed with the Bayley Scales of Infant Development-II 1 and 3 months after the injury. Nearly half of the injured children showed persisting deficits in attention/arousal, emotional regulation and motor coordination. Greater injury severity, as indicated by lower coma scale scores, longer periods of unconsciousness and the presence of edema/cerebral infarctions was associated with poorer outcomes in all domains.
Thrombosis of the Internal Carotid Artery Secondary to Soft Palate Injury in Children and Childhood
Authors: Borges Guilherme , Bonilha Leonardo , Santos Starlynn F. , Carelli Edmur F. , Fernandes Yvens B. , Ramina Ricardo , Zanardi Verônica , Menezes José R. , Nogueira Roberto J.N.
Published: April 2003

Trauma to the soft palate is a uncommon event during childhood. Stroke following intraoral trauma is also rare, but has been well documented by the current literature as a potentially serious complication. In this article, we report 2 cases of posttraumatic internal carotid artery thrombosis depicted by imaging studies. We discuss pathogenesis, and the literature is reviewed.
Parathyroid-Hormone-Related-Protein-Producing Thymic Carcinoma Presenting as a Giant Extrathoracic Mass
Authors: Suzuki Kazuhiko , Tanaka Hiroshi , Shibusa Takashi , Shibuya Yoshie , Inuzuka Manabu , Fujishima Takuya , Abe Shosaku
Published: April 2003

A 53-year-old female with a 9-month history of chest pain presented with a giant anterior chest wall mass. Radiologic examination showed an anterior mediastinal tumor invading the chest wall. Serum calcium and parathyroid hormone-related protein (PTHrP) levels were extremely elevated. Biopsy specimens disclosed a squamous cell carcinoma with Hassall’s corpuscle-like keratotic pearls, and an immunohistological study showed a positive staining with PTHrP. The tumor and serum PTHrP concentration markedly decreased following cisplatin-based chemotherapy and radiation. This is the first case of PTHrP producing a thymic carcinoma with the unusual presentation of a large extrathoracic mass.
Effect of Dietary Supplementation with Polyunsaturated Fatty Acids on Bronchial Hyperreactivity in Subjects with Seasonal Asthma
Authors: Villani F. , Comazzi R. , De Maria P. , Galimberti M.
Published: April 2003

Dietary supplementation with omega-3 essential fatty acids results in the production of uniqe 5-lipoxygenase and cyclooxygenase products which are biologically less active and may inhibit the production, or actions, of the eicosanoids produced when arachidonic acid is the substrate for 5-lipoxygenase and cyclooxygenase, rather than omega-3 essential fatty acids. Since airway inflammation may play a central role in the pathophysiology of asthma, we studied the effect of omega-3 essential fatty acids on bronchial responsiveness in 7 atopic patients suffering from seasonal asthma due to airborne allergens, and positive to intracutaneous skin reaction to two or more allergens. Bronchial responsiveness to ultrasonically nebulized distilled water (UNDW) was determined 30 days from the initial ingestion of 3 g/day of omega-3 essential fatty acids and 30 days after stopping dietary supplementation. Flow volume curves and Raw were recorded before the provocation test, at the end of inhalation, and at 10-, 20-, 30- and 60-min intervals. The maximum fall in forced expiratory volume in 1 s (FEV1) and the maximum increase in airway resistance (Raw) were chosen as the main outcome parameters. After 30 days of dietary supplementation, bronchial responsiveness to UNDW was significantly improved (in fact maximum fall in FEV1 was –11% vs. –28% before treatment, and maximum increase in Raw was +37% vs. +265% before treatment). The challenge test repeated 30 days after stopping dietary supplementation was the same as that recorded before treatment. The present data strongly suggest the hypothesis that dietary supplementation with omega-3 essential fatty acids could decrease bronchial hyperreactivity in atopic patients.
Is Asthma in the Elderly Really Different?
Authors: Quadrelli Silvia A. , Roncoroni Aquiles J.
Published: April 2003

To examine the nature of asthma in the elderly, we compared older (group 1: 65 years or older, n = 50) with younger patients (group 2: <40 years, n = 99) and to determine the influence of long-standing disease, elderly asthmatics with early onset (group A: onset before 40, n = 22) were compared with patients developing symptoms later in their lives (group B: onset after 40, n = 22). Blood eosinophilia and IgE value ≥100 IU/l were more frequent in younger patients. Short symptom-free periods were more frequent among older asthmatics (78.5 vs. 45.4%, p < 0.001). Only 31.2% of older patients had only mild symptoms. Requirement of systemic steroids was higher in the elderly population. The worst FEV1 was lower in older patients (54.4 ± 17.3 vs. 71.8 ± 18.5%, p {FC96}& 0.001). Patients with early-onset asthma showed more frequently shorter symptom-free periods (93.3 vs. 53.3%, p <0.05), higher emergency admissions/year, and hospitalizations/year. Best FEV1 (group 1: 66.7 ± 13.7% vs. group 2: 90.3 ± 15.1%, p < 0.005) and worst FEV1 (46.2 ± 13.1 vs. 61.0 ± 13.2%, p < 0.01) were lower in early-onset patients. A higher systemic steroid requirement, a lower best and worst FEV1, shorter symptom-free periods and a lesser proportion of patients with only mild symptoms were observed in patients older than 65 with early-onset asthma compared with those younger than 40 years. Elderly patients with a shorter duration of asthma were not different from young patients. Our study strongly suggests that severity of asthma and development of irreversible airflow obstruction depend on the duration of disease.
Waldenström’s Macroglobulinemia with Pulmonary Amyloidosis
Authors: Zatloukal Petr , Bezdíček Petr , Schimonová Marta , Havlíček František , Tesařová Petra , Slováková Alena
Published: April 2003

We present a case of AL-type amyloidosis involving pulmonary parenchyma and hilar and mediastinal lymph nodes in a patient with Waldenström’s macroglobulinemia. Direct infiltration of pulmonary parenchyma by lymphocytes and plasma cells is an important factor in the etiology and pathogenesis of pulmonary manifestations of the disease. Despite detailed examination, we did not find amyloid depositions in any extrapulmonary site.
Changing Ventilator: An Option to Take into Account in the Treatment of Persistent Vomiting duringNasal Ventilation
Authors: DíazLobato Salvador , GarciaTejero Maria Teresa , RuizCobos Angeles , Villasante Carlos
Published: April 2003

Problems related with nasal intermittent positive pressure ventilation (NIPPV) are nasal and mouth dryness, soreness on the bridge of the nose, eye irritation and epistaxis. Gastrointestinal distention due to air swallowing has been reported in half of the patients. Acceleration of digestive function with drugs or reduction of the volume delivered to alleviate gastric distension are considered as the conventional treatment. It is also possible that the problem disappears spontaneously after a few weeks of NIPPV. We present a patient in whom conventional treatment was unsuccessful. When we changed to a different ventilator, symptoms disappeared, and the new one was very well tolerated. In our experience, changing ventilators should be included in the management of gastrointestinal distension due to NIPPV, especially if conventional procedures, such as drugs or gas flow modifications, fail.
Lactate Dehydrogenase in Bronchoalveolar Lavage Fluid of Patients with Active Pulmonary Tuberculosis
Authors: Emad Ali , Reza Rezaian Gholam
Published: April 2003

Background: Serum lactate dehydrogenase (LDH) concentration is an indicator of tissue injury. It may be increased in a variety of interstitial diseases and in pulmonary tuberculosis (PTB). Objective: To investigate the value of LDH levels in bronchoalveolar lavage fluid (BALF) for the diagnosis of active PTB and to assess its relationship with serum LDH levels. Methods: The study was a prospective clinical study. It included 25 consecutive patients with documented active PTB and 20 healthy adults who underwent bronchoscopy with bronchoalveolar lavage (BAL). Both total serum and LDH levels were measured. Results: BALF LDH level was increased in all patients with active PTB. The mean BALF LDH level was significantly higher in patients with PTB (198.84 ± 88.31 mIU/ml) as compared to controls (14.01 ± 8.69 mIU/ml) (p = 0.0001). There was a significant correlation between BALF LDH and serum LDH levels in patients with PTB (r = 0.55, p = 0.006). Conclusion: BALF LDH levels are not specific and may be increased in many diseases. A very low value (possibly less than 60 mIU/ml) may, on the other hand, be useful to exclude the diagnosis of active PTB.
Mesalazine-Induced Eosinophilic Pneumonia
Authors: Tanigawa Ken , Sugiyama Keiichi , Matsuyama Hiromi , Nakao Hideto , Kohno Kenji , Komuro Yasuaki , Iwanaga Yoshijiro , Eguchi Katsumi , Kitaichi Masanori , Takagi Hiroyuki
Published: April 2003

A 35-year-old woman with a 6-month history of ulcerative colitis and treatment with oral mesalazine (5-aminosalicylic acid) developed dry cough, low-grade fever and bilaterally wandering pulmonary infiltrates. Improvement in clinical symptoms and radiological abnormalities occured spontaneously after discontinuation of mesalazine. The transbronchial lung biopsy demonstrated the organizing stage of eosinophilic pneumonia. Drug lymphocyte stimulation test was positive for mesalazine and negative for sulfasalazine and sulfapyridine. The present case indicates that although mesalazine-induced eosinophilic pneumonia is an extremely rare entity, its possibility should be fully considered in patients developing unexplained respiratory symptoms while on mesalazine therapy.
A Chest Wall Restrictor to Study Effects on Pulmonary Function and Exercise
Authors: Cline CamalaC. , Coast J.Richard , Arnall DavidA.
Published: April 2003

Chest wall-restrictive loading reduces a person’s ability to expand the chest wall during inhalation and results in decrements in lung capacities, resting pulmonary function, and ultimately, exercise performance. Chest wall restriction is observed in some forms of skeletal and pulmonary diseases (e.g., scoliosis) as well as in occupational situations (e.g., bulletproof vests). We have designed a constant-pressure chest wall-restrictive device that provides a quantifiable and reproducible load on the chest. This paper describes the device and the initial pulmonary function tests conducted. Ten subjects participated in this study. Subjects wore the restrictive device while performing pulmonary function tests at four externally added restrictive loads on three separate occasions. A two-way repeated-measures multivariate analysis of variance revealed significant decreases in forced expiratory vital capacity (FVC) and forced expiratory volume in 1 s (FEV1.0) at each load while the ratio of FEV1.0 to FVC (FEV1.0%) was maintained. No significant differences in any variable were found across time or between the seated and standing position. These results indicate that this chest wall-restrictive device provides a quantifiable added inspiratory load in the breathing cycle that results in reproducible decrements in pulmonary function representative of those seen in some restrictive pulmonary disease and occupational situations.
Hypersensitivity Pneumonitisamong Workers CultivatingTricholoma conglobatum (Shimeji)
Authors: Akizuki Norikazu , Inase Naohiko , Ishiwata Nobuo , Jin Yasuto , Atarashi Kenichi , Ichioka Masahiko , Yoshizawa Yasuyuki , Marumo Fumiaki
Published: April 2003

We report five cases of hypersensitivity pneumonitis among workers cultivating Tricholoma conglobatum (shimeji). After having worked for 5 to 20 years, they began to notice symptoms of cough, sputum, and dyspnea. They were diagnosed as having a hypersensitivity pneumonitis based on clinical features, bronchoalveolar lavage and transbronchial lung biopsy. By the double immunodiffusion test, precipitating lines between shimeji spore antigen and sera were observed in all of the patients. By enzyme-linked immunosorbent assay, the antibody activities against shimeji and three species of fungi (Cladosporium sphaerospermum, Penicillium frequentans, and Scopulariopsis species) were significantly higher in the sera of the patients than in those of normal subjects who were cultivating shimeji. Although it is not clear what causes this disease, these findings may be helpful in determining the specific antigen.
Antineutrophil Cytoplasmic Antibodies in Diffuse Panbronchiolitis
Authors: Sugiyama Yukihiko , Kitamura Satoshi
Published: April 2003

Background: There are some reports of the coexistence of chronic suppurative lung diseases such as cystic fibrosis and systemic vasculitis. Diffuse panbronchiolitis has the same characteristics as chronic recurrent sinopulmonary infection and respiratory bronchiolitis. Methods: Serum samples from 30 patients with diffuse panbronchiolitis and 57 patients with other pulmonary diseases were tested to find the titer of myeloperoxidase antineutrophil cytoplasmic antibodies (MPO-ANCA). Results: We found MPO-ANCA positivity in 4 patients with diffuse panbronchiolitis but not in those with other pulmonary diseases. Conclusions: Our findings show that MPO-ANCA is positive in some patients with diffuse panbronchiolitis. Careful attention should be paid to the combination of chronic pulmonary infection and various vasculitis.
Substance P Relaxes Rat Bronchial Smooth Muscle via Epithelial Prostanoid Synthesis
Authors: Bodelsson Mikael , Blomquist Sten , Caverius Kai , Törnebrandt Kenneth
Published: April 2003

Background: Substance P is present in bronchial nerve fibres. The physiological actions of substance P are mediated via tachykinin NK1 receptors. Immunochemical studies have demonstrated tachykinin NK1 receptors in the rat airway epithelium. Objective: To elucidate how epithelial tachykinin NK1 receptors affect smooth muscle response to substance P. Methods: Contractile response of isolated rat bronchial trunk with or without epithelium was recorded. Results: In intact segments precontracted by 5-hydroxytryptamine, relaxation was induced by substance P and the nitric oxide donor, sodium nitroprusside. Removal of the epithelium abolished relaxation induced by substance P but did not affect relaxation induced by sodium nitroprusside. The cyclo-oxygenase inhibitor, indomethacin, but not the nitric oxide synthase inhibitor, L-NG-monomethylarginine, reduced the relaxation in response to substance P. Conclusions: Epithelial tachykinin NK1 receptors mediate substance-P-induced relaxation of rat bronchial smooth muscle via release of prostanoids but not nitric oxide.
German Version of the Epworth Sleepiness Scale
Authors: Bloch Konrad E. , Schoch Otto D. , Zhang Jinnong N. , Russi Erich W.
Published: April 2003

Background: The Epworth Sleepiness Scale (ESS) is a questionnaire widely used in English speaking countries for assessment of subjective daytime sleepiness. Objective: Our purpose was to translate and validate the ESS for use in German-speaking countries. Methods: A German translation of the ESS was administered to 159 healthy German-speaking Swiss and to 174 patients with various sleep disorders. Results: The mean ± SD of ESS scores in normals was 5.7 ± 3.0, in patients it was 13.0 ± 5.1 (p < 0.001). Scores were not correlated with age or gender but with the percentage of time spent at an oxygen saturation <90% (R = 0.35, p < 0.001), and the respiratory disturbance index (R = 0.26, p < 0.001) in primary snorers and sleep apnea patients. Item analysis confirmed internal consistency of the scale (Cronbach α = 0.60 in normals, and 0.83 in patients). Follow-up scores in 25 sleep apnea patients on treatment showed a reduction by 7 ± 5 points (p < 0.05). Conclusions: Our data validate the ESS for application in German-speaking populations. The simplicity, reliability and the apparent lack of relevant influences of language and cultural background on performance of the ESS makes it a valuable tool for clinical management and research.
Length and Lead Time Biases in Radiologic Screening for Lung Cancer
Authors: Soda H. , Oka M. , Tomita H. , Nagashima S. , Soda M. , Kohno S.
Published: April 2003

Objective: Our goal was to investigate whether the length and lead-time biases of radiologic screening for lung cancers vary according to the histologic type of the tumor. Methods: We analyzed the survival rates and radiographs of 119 cases of adenocarcinomas-large-cell carcinomas (ALC) and 50 peripheral squamous cell carcinomas (PSQ) detected in 205,401 screened individuals. Results: The sensitivity of screening and 5-year survival rates were 84.0% and 48.2% for ALC, and 52.0% and 18.5% for PSQ, respectively. The corrected length bias was 4.3% for ALC and 4.6% for PSQ. Stage III-IV ALC was often identified on 1-year-old films, but stage III-IV PSQ was not. Half of stage I ALC presented 2 or more years before detection, while half of stage I PSQ appeared within 1 year before detection. The survival rate of nonresected cases with stage I ALC was decreased 4 years after detection, while that of nonresected cases with stage I PSQ was decreased just after detection. The period of stage I ALC and PSQ was at least 6 years and 1 year, respectively. Conclusions: Slowly growing ALC had high sensitivity in radiologic screening and a high rate in 5-year survival, but had long lead time and delay in detection. PSQ grew rapidly resulting in low sensitivity in radiologic screening, and short lead time and survival. In both types, the magnitude of corrected length bias was not remarkable. The survival of ALC should be carefully evaluated because of the long lead time.