bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacological Modulation of LPS-Induced MIP-1α Production by Peripheral Blood Mononuclear Cells
Authors: Kimata Masahiro , Shichijo Michitaka , Daikoku Michio , Inagaki Naoki , Mori Hiroshi , Nagai Hiroichi
Published: April 2003

In the present study, we investigated the effects of some anti-asthmatic drugs on the production of the CC chemokine, macrophage inflammatory protein-1α (MIP-1α), in response to lipopolysaccharide (LPS) by peripheral blood mononuclear cells (PBMC). MIP-1α production was induced by LPS in a concentration-dependent fashion and reached the maximum at 10 µg/ml LPS (27.5±2.3 ng MIP-1α/106 PBMC). At a submaximal concentration of LPS (1 µg/ml), the release of MIP-1α increased with time and reached the maximum 24 h after LPS stimulation. Actinomycin D and cycloheximide inhibited MIP-1α production completely, but glucocorticoids did not completely inhibit MIP-1α production, with a maximum inhibition of 70%. We examined the effect of β-stimulants and phosphodiesterase inhibitors, which upregulate intracellular cyclic AMP levels, on MIP-1α production. When PBMC were treated with β-stimulants alone, β-stimulants showed a slightly inhibitory effect on MIP-1α production. However, the coadministration of roliplam significantly potentiated the inhibitory effect of β-stimulants on MIP-1α production. Moreover, db-cAMP suppressed MIP-1α production dose-dependently. The above data indicate that the production of MIP-1α is regulated by cyclic AMP and that cyclic AMP could provide a useful target for therapeutic treatment in asthmatic diseases and other diseases where MIP-1α is involved in their etiology.
The Contractile Effect of Fedotozine on Guinea Pig Isolated Intestinal Cells Is Not Mediated by Kappa Opioid Receptors
Authors: Coruzzi G. , Morini G. , Coppelli G. , Bertaccini G.
Published: April 2003

The compound fedotozine, recently described as a peripheral kappa opioid receptor agonist, was tested on smooth muscle cells isolated from the longitudinal muscle layer of the guinea pig ileum, in comparison with the selective kappa receptor agonist, compound U-50488. Fedotozine (1 nmol/l–1 µmol/l) caused a concentration-dependent contraction of intestinal cells, with a maximum decrease in cell length not significantly different from that caused by acetylcholine. The kappa agonist U-50488 (0.1 pmol/l–100 nmol/l) was without effect. The contractile effect of fedotozine was not significantly modified by naloxone (0.1–1 µmol/l). These results indicate that fedotozine can have direct excitatory effects on intestinal smooth muscle cells from the guinea pig ileum not mediated by activation of kappa opioid receptors.
Effects of Ketoconazole on Digoxin Absorption and Disposition in Rat
Authors: Salphati Laurent , Benet Leslie Z.
Published: April 2003

Digoxin, a cardiac glycoside, is a substrate of the multidrug transporter P-glycoprotein (Pgp), and in rats has also been identified as a substrate for cytochrome P450 3A (CYP3A). Ketoconazole, an antifungal agent, was shown to inhibit Pgp in a multidrug-resistant cell line, and is known to be a potent inhibitor of CYP3A. Here, we determined the effects of ketoconazole on digoxin absorption and disposition in rats. Digoxin was administered intravenously or orally with or without a concomitant oral dose of ketoconazole. When given intravenously, digoxin AUC increased from 93 ± 22 to 486 ± 26 µg·h/l with ketoconazole administration. Similarly, ketoconazole raised the AUC of orally administered digoxin from 63 ± 17 to 411 ± 50 µg·h/l. Concomitant ketoconazole administration prolonged digoxin elimination, yielding a nonlinear pharmacokinetic profile. Using time-averaged values, digoxin bioavailability increased from 0.68 ± 0.18 to 0.84 ± 0.10, while mean absorption time was reduced from 1.1 ± 0.4 to 0.3 ± 0.1 h. Thus, in rats, ketoconazole increases digoxin plasma concentrations, rate of absorption and bioavailability. Although the effects of ketoconazole on AUC could be explained by inhibition of both CYP3A and Pgp, which cannot be differentiated in this study, the decreased mean absorption time can only be explained by inhibition of Pgp in the intestine.
A Method for Measuring Naringenin in Biological Fluids and Its Disposition from Grapefruit Juice by Man
Authors: Lee Yil Seob , Reidenberg Marcus M.
Published: April 2003

The major flavonoid in grapefruit juice, naringin, has an aglycone, naringenin, that inhibits some oxidations in vitro and may have in vivo activity. We developed an HPLC method to measure naringenin using a methanol:water mobile phase with UV absorbance detection. The recovery of naringenin was 96%. Two subjects who drank grapefruit juice containing 214 mg naringin daily excreted approximately 30 mg/day of naringenin glucuronide. Thus, naringin is hydrolyzed to naringenin and then conjugated with glucuronic acid prior to excretion of the conjugate.
Predictive Sensitivity of Human Cancer Cells in vivo Using Semipermeable Polysulfone Fibers
Authors: Chu Ming Y.W. , Lipsky Milton H. , Yee Lorrin K. , Epstein John , Whartenby Katharine A. , Freeman Scott , Chen Tian M. , Chu Edward , Forman Edwin N. , Calabresi Paul
Published: April 2003

An in vivo experimental model was developed to predict efficiently and accurately chemosensitivity of human tumors. Human cancer cells either from cultured cell lines or from patients’ tumors were injected directly into semipermeable polysulfone fibers subsequently implanted into immunocompetent rats. Results suggest utility of this novel model system for predicting tumor sensitivity to a wide range of anticancer agents and for potentially guiding the treatment of cancer patients in the clinical setting.
Site-Specific Effects of the Nonsteroidal Anti-Inflammatory Drug Lysine Clonixinate on Rat Brain Opioid Receptors
Authors: Ortí Eduardo , Coirini Héctor , Pico José Carlos
Published: April 2003

In addition to effects in the periphery through inhibition of prostaglandin synthesis, several lines of evidence suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) act in the central nervous system. The possibility that the central action of NSAIDs involves regulation of opioid receptors was investigated by quantitative autoradiography of mu, delta, and kappa sites in rat brain slices. Increased (p < 0.05) labeling of mu receptors was observed in thalamic nuclei, gyrus dentate, and layers of the parietal cortex of rats treated for 10 days with lysine clonixinate. Labeling of delta receptors was lower in the lateral septum, and kappa sites decreased in thalamic nuclei. These effects were not mediated through direct interaction with opioid-binding sites, since receptor-binding assays using rat brain membranes confirmed that clonixinate up to 1 × 10–4 mol/l does not inhibit mu, delta, and kappa receptor specific binding. Central effects of NSAIDs might, therefore, involve interaction with the opioid receptor system through indirect mechanisms.
Age-Related Expression of Renal Thrombospondin 1 mRNA in F344 Rats: Resemblance to Diabetes-Induced Expression in Obese Zucker Rats
Authors: Olson B.A. , Day J.R. , Laping N.J.
Published: April 2003

Age-related increases occurred in renal thrombospondin 1 (TSP1) mRNA in F344 rats, resembling diabetes-induced TSP1 mRNA in the obese Zucker rat. TSP1 mRNA was 3.5-fold higher in 24-month-old than in 3-month-old F344 rats. TSP1 mRNA increased similarly in 5-month-old obese Zucker rats as compard with lean littermates and correlated positively with the extent of proteinuria (r = 0.71). In situ hybridization identified elevated TSP1 mRNA levels in epithelial cells of distended tubules as well as in interstitium near dilated tubules of both 24-month-old F344 rats and 5-month-old obese Zucker rats. Furthermore, thrombin increased TSP1 mRNA in mesangial and epithelial cells in culture, indicating that thrombin may contribute to elevated TSP1 expression in renal disease. Thrombin increased TSP1 mRNA within 30 min after treatment which required de novo synthesis of protein. The thrombin receptor tethered ligand peptide, SFLLRN, increased TSP1 mRNA, indicating that the thrombin-induced increase in TSP1 mRNA was due to direct thrombin receptor (PAR1) stimulation. These results show that increased TSP1 mRNA levels are a component of interstitial fibrosis seen in aged and diabetic kidneys and suggest that similar pathological changes occur in kidneys of aging and diabetic rats.
Effects of Zinc Acexamate (NAS-501) on Superoxide Radicals and Lipid Peroxidation of Rat Gastric Mucosa
Authors: Tsutsui Yasuhiro , Nakamura Yukio , Yamaguchi Shiho , Kawanaka Nobuyo , Sato Makoto
Published: April 2003

Zinc acexamate (NAS-501), an anti-ulcer agent, has been reported to prevent various acute experimental gastric mucosal lesions and duodenal ulcers in rats. In order to clarify the mechanisms by which NAS-501 exhibits the anti-ulcer effects, we investigated the anti-oxidative effects of NAS-501 in vitro and in vivo. NAS-501 significantly reduced the superoxide radical-dependent chemiluminescence, generated by hypoxanthine-xanthine oxidase, rat neutrophils and guinea-pig macrophages in vitro. These in vitro effects were also confirmed by electron spin resonance using a 5,5-dimethyl-1-pyrroline-N-oxide spin-trapping method. In addition, NAS-501 significantly inhibited lipid peroxidation induced by increasing concentrations of Fe2+/ascorbate in rat gastric mucosal homogenate in vitro. Oral administration of NAS-501 (30 mg/kg) significantly inhibited production of thiobarbituric acid-reactive substance in rat gastric mucosa following per os instillation of 60% ethanol in 150 mmol/l HCl in vivo. These results suggest that NAS-501 exhibits the preventive effect from acute gastric mucosal lesions by the anti-oxidative activity.
Reduction by ATP-Sensitive Potassium Channel Opener, YM934, of Experimental Myocardial Infarct Size in Anesthetized Dogs
Authors: Taguchi Taku , Uchida Wataru , Takenaka Toichi , Takeo Satoshi
Published: April 2003

The present study was undertaken to examine whether the ATP-sensitive potassium channel opener, YM934, would be effective in reducing infarct size in a model of myocardial infarction in anesthetized dogs. For this purpose the effects of nifedipine, a calcium channel blocker, and hydralazine, a vasodilator with unknown mechanisms, were also investigated for comparison. Severe, irreversible myocardial injury was produced by a 90-min occlusion of the proximal left anterior descending coronary artery followed by 5 h of reperfusion. Infusion of YM934 (0.1 μg/kg/min i.c.) during the last 15 min of pre-ischemia reduced the myocardial infarct size and attenuated the release of creatine kinase MB eluted from the hearts without alteration in hemodynamic parameters including regional myocardial blood flow. In contrast, the other vasodilators, hydralazine and nifedipine, did not reduce myocardial infarct size under the same coronary vasodilatory conditions. These observations indicate that intracoronary YM934 is cardioprotective and that this effect is independent of alterations in regional myocardial blood flow.
The Antihypertensive Effect of the Berberine Derivative 6-Protoberberine in Spontaneously Hypertensive Rats
Authors: Liu Ju-Chi , Chan Paul , Chen Yi-Jen , Tomlinson Brian , Hong Sheu-Fang , Cheng Juei-Tang
Published: April 2003

Berberine is a natural isoquinoline alkaloid found in plants of the Ranunculaceae and Berberidaceae families. Extracts from berberine-containing plants have been used as traditional Chinese folk remedies for centuries. The antihypertensive effects of the berberine derivative 6-protoberberine (PTB-6) were studied in spontaneously hypertensive rats (SHRs). In conscious SHRs, PTB-6 lowered the systolic blood pressure in a dose-dependent manner (6-PTB: 5 mg/kg, –31.1 ± 1.6 mm Hg; 10 mg/kg, –42.4 ± 3.1 mm Hg). Cardiac output using the thermodilution method was reduced in PTB-6-treated anesthetized SHRs with a tendency to decrease in heart rate. Injection of PTB-6 into the intracerebral ventricles of SHRs lowered the systolic arterial blood pressure and heart rate. The berberine derivative PTB-6 is an effective antihypertensive agent. The mechanism of the antihypertensive effect of PTB-6 is probably through a central sympatholytic effect.
Altered Relaxant Responses to Adenosine and Adenosine 5′-Triphosphate in the Corpus cavernosum from Men and Rats with Diabetes
Authors: Gür Serap , Öztürk Bülent
Published: April 2003

The present study was aimed at investigating the effects of diabetes on the cavernosal smooth muscle relaxations mediated by adenosine and adenosine triphosphate (ATP) in tissues obtained from men and rats. Adenosine- and ATP-induced relaxant responses showed an enhanced sensitivity with an unaltered effectiveness in diabetic men. Adenosine-elicited relaxation in diabetic rat corporeal tissues exhibited enhanced effectiveness with unaltered sensitivity, whereas ATP-induced relaxations were decreased in diabetic animals when compared to control animals. Tetraethylammonium pretreatment, but not glibenclamide, L-NAME and 8-phenyltheophylline, normalized enhanced apparent affinity to adenosine in tissue from diabetic men and effectiveness (Emax) to adenosine in diabetic rats. These results suggest that adenosine-elicited relaxation in diabetes is controlled at the receptor level events including K+ channels in men whereas in rats postreceptor-related events including K+ channels control the adenosine-induced relaxation. These relaxations to adenosine and ATP in men and rats with and without diabetes may be nitric oxide-independent mechanisms. Our results also suggest that ATP-induced relaxation did not involve KATP channels and Ca-activated K+ channels.
Kallikrein-Kinin System in Acute Pancreatitis: Potential of B2-Bradykinin Antagonists and Kallikrein Inhibitors
Authors: Griesbacher Thomas
Published: April 2003

The development of selective antagonists for bradykinin B2 receptors has greatly advanced research on the role of the kallikrein-kinin system in acute pancreatitis. Kinins released during the course of the inflammatory injury are the major cause of the vascular symptoms, i.e. pancreatic oedema formation and its consequences, such as haemoconcentration, hypovolaemia and hypotension. Kinins are also involved in the accumulation of potentially cytotoxic factors in the pancreatic tissue. However, treatment with B2 antagonists must begin prior to the formation of pancreatic oedema in order to inhibit or attenuate the vascular effects. Visceral pain as a possible target symptom for treatment with B2 antagonists at later time points is suggested by the B2 receptor-mediated activation of nociceptive afferents.
Effect of Nabumetone Treatment on Vascular Responses of the Thoracic Aorta in Rat Experimental Arthritis
Authors: Ülker Sibel , Önal Aytül , Hatip Funda Bölükbaşı , Sürücü Ayşe , Alkanat Murat , Koşay Sezen , Evinç Akgün
Published: April 2003

Nabumetone is a nonsteroidal anti-inflammatory (NSAI) drug which is known to cause less gastrointestinal damage than other NSAI drugs. This study was performed to evaluate whether nabumetone treatment might alter the vascular aberrations related to inflammation in a rat model of adjuvant-induced arthritis. Nabumetone treatment (120 or 240 mg·kg–1·day–1, orally) was initiated on the 15th day of adjuvant inoculation and continued for 14 days. Arthritic lesions, vascular contractile and relaxant responses and gastroduodenal histopathological preparations were evaluated 29 days after adjuvant inoculation. The contractile responses of aortic rings to phenylephrine and KCl were increased in grade 2 arthritic rats. In grade 3 arthritis only the phenylephrine contractility was decreased. The relaxant responses to acetylcholine and sodium nitroprusside were decreased in grades 2 and 3. In healthy rats, nabumetone did not change the vascular responses. After treatment of arthritic rats with nabumetone, both the contractile and relaxant response of the aortic rings returned to normal, and arthritic score and paw swelling were reduced. Gastroduodenal histopathology did not show erosions or ulcers in any of the groups. In conclusion, nabumetone improved the systemic signs and vascular alterations in experimental arthritis without showing any gastrointestinal side effects.
Participation of Neuropeptides in Antigen-Induced Contraction of Guinea Pig Bronchi via NK2 but Not NK1 Receptor Stimulation
Authors: Tanpo Takashi , Nabe Takeshi , Yasui Kiyoshi , Kamiki Toshihisa , Kohno Shigekatsu
Published: April 2003

We evaluated the contribution of neuropeptides to antigen-induced contractions of isolated bronchi and tracheae of passively sensitized guinea pigs using CP-96345 and SR 48968, specific antagonists of NK1 and NK2 receptors, respectively, in combination with treatment by an antihistaminic and a cysteinyl leukotriene antagonist. SR-48968 but not CP-96345, significantly inhibited the late phase of the bronchial contraction. Phosphoramidon, a neutral endopeptidase inhibitor, tended to potentiate bronchial contraction. Posttreatment with SR-48968 decreased the enhanced contraction induced by the inhibitor as well as the nonenhanced contraction to similar levels of tension. On the other hand, antigen-induced tracheal contraction was not altered by either neuropeptide antagonist. These results suggest that neuropeptides mediate the antigen-induced contractile response of the guinea pig bronchus partly through NK2 receptor stimulation.
Effects of Propylthiouracil Treatment on Antioxidant Activities in Blood of Toxic Multinodular Goiter Patients
Authors: Özdem Sebahat , Alicigüzel Yakup , Özdem Sadi , Karayalçin Ümit
Published: April 2003

Erythrocyte, serum and plasma antioxidant activities and the effects of propylthiouracil (PTU) treatment on these activities were studied in patients with toxic multinodular goiter. The activities of the erythrocyte antioxidant enzymes (glucose-6-phosphate dehydrogenase, catalase, Cu/Zn-superoxide dismutase, selenium (Se)-dependent glutathione peroxidase and glutathione reductase) and the levels of erythrocyte Se, serum ceruloplasmin and plasma malondialdehyde were significantly higher while serum vitamin E, plasma vitamin C and plasma Se were lower in hyperthyroid patients. PTU treatment, not for 1 but for 3 months caused a partial reversal of antioxidant activities to euthyroid levels. It is suggested that alterations in blood antioxidant activities following PTU treatment might be due to the antioxidant and/or antithyroid effect of this drug.
Site-Directed Mutagenesis Implicates a Threonine Residue in TM6 in the Subtype Selectivities of UH-AH 37 and Pirenzepine at Muscarinic Receptors
Authors: Ellis John , Seidenberg Margaret
Published: April 2003

The structural basis for the selectivity of the antagonist UH-AH 37 at human muscarinic acetylcholine receptors was investigated by expressing mutant receptors in COS-7 cells. Previous studies have demonstrated that the interaction between UH-AH 37 and [3H]N-methylscopolamine in equilibrium assays is competitive and that the high affinity of UH-AH 37 for the M5 subtype, compared to M2, is due to an epitope in the sixth transmembrane domain (TM6) or the third outer loop of the receptor. By mutating each nonconserved residue in this region of M2 and M5 to its counterpart in the other receptor, we identified a threonine residue in the middle of TM6 uniquely responsible for the higher affinity of the M5 receptor (M1, M3, and M4 receptors also carry a threonine at that location and also have high affinity for UH-AH 37). The mutant receptor in which the corresponding alanine of the M2 receptor was replaced by threonine, M2401ala ⇒ thr, expressed enhanced affinity for pirenzepine as well as for UH-AH 37. The chick M2 receptor, which expresses anomalously high affinity for pirenzepine, differs from its mammalian counterparts by the presence of a threonine at this position. Affinities of AF-DX 116 and 4-DAMP, as well as the allosteric potency of UH-AH 37, were not sensitive to the M2401 ala ⇒ thr mutation.
Bimodal Expression of CYP2D16 in the Guinea Pig Adrenal Cortex
Authors: Colby Howard D. , Huang Yajue , Jiang Qinshi , Voigt Jeffrey M.
Published: April 2003

Prior studies revealed an apparent bimodal distribution of adrenal xenobiotic-metabolizing activities in outbred guinea pigs. High activities were characteristic of most animals but a minority had very low rates of metabolism. The present studies were done to determine the basis for this distribution. Among the enzymatic activities abundant in guinea pig adrenal microsomes is bufuralol 1′-hydroxylation, a marker for CYP2D isozymes. Western blot analyses revealed that adrenal expression of CYP2D16, the guinea pig CYP2D analogue, was highly correlated with xenobiotic-metabolizing activities. Of 12 animals studied, 4 had low levels of adrenal CYP2D16 expression and correspondingly low bufuralol 1′-hydroxylase and benzphetamine N-demethylase activities. In contrast, adrenal expression of steroidogenic P450 isozymes (CYP17 and CYP21) and the corresponding steroid hydroxylase activities were similar in all animals. There was also no evidence of polymorphism in hepatic xenobiotic metabolism. The results suggest that the bimodal expression of adrenal CYP2D16 is at least partly responsible for the variability in adrenal xenobiotic metabolism, and that this pattern of expression is not applicable to other adrenal P450 isozymes or to hepatic CYP2D16. Further studies are needed to determine if genetic polymorphism is responsible for the mode of adrenal CYP2D16 expression.
The Evolution of Drug Metabolism
Authors: Nebert Daniel W. , Dieter Matthew Z.
Published: April 2003

So-called ‘drug-metabolizing enzyme’ (DME) genes have existed on this planet for more than 2.5 billion years and would be more appropriately named ‘effector-metabolizing enzymes’. Genes encoding DMEs have functioned in many fundamental processes in prokaryotes and, more recently, in countless critical life processes in plants and animals. DME genes exist in every eukaryotic cell and in most, if not all, prokaryotes. Over the past decade, it has become clear that each person has their own ‘individual fingerprint’ of unique alleles coding for DMEs. The underlying genetic predisposition of each patient reflects combinations of poor- and extensive-metabolizer phenotypes. If these enzymes cooperate in the same metabolic pathway for any given drug or environmental agent, such ecogenetic variability might be synergistic and could cause 30- to >40-fold differences in activation or degradation. The end result can be large interindividual differences in risk of environmentally caused toxicity or cancer. Human DME gene polymorphisms often show high frequencies of variant alleles. Many factors contribute to persistence of these high frequencies, including a combination of selective pressures involving diet, climate and geography, as well as ‘balanced polymorphisms’ (‘shared benefit’ for the heterozygote). However, the extensive heterogeneity in the human genome currently being discovered suggests many more polymorphisms will occur not only in drug metabolism genes, but in all genes, and exhibiting large gene-by-gene variability.
Genetic Polymorphism of Thiopurine S-Methyltransferase: Molecular Mechanisms and Clinical Importance
Authors: Krynetski Eugene Y. , Evans William E.
Published: April 2003

The activity of thiopurine S-methyltransferase (TPMT) is inherited as an autosomal co-dominant trait. In most large world populations studied to date, approximately 10% of the population have intermediate activity due to heterozygosity at the TPMT locus, and about 0.33% is TPMT deficient. TPMT is now one of the most well characterized genetic polymorphisms of drug metabolism, with the genetic basis having been well defined in most populations, providing molecular strategies for studying this genetic polymorphism in human and experimental models. Three mutant alleles, TPMT*2, TPMT*3A and TPMT*3C, account for the great majority of mutant alleles in all human populations studied to date. Significant ethnic differences occur in the frequencies of these mutant alleles. Progress in DNA analysis has made it practical to use genotyping techniques for the molecular diagnosis of TPMT deficiency and heterozygosity, thereby avoiding adverse effects that are more prevalent in TPMT-deficient and heterozygous patients prescribed thiopurine medications.
Cardiovascular Responses to NMDA Injected into Nuclei of Hypothalamus or Amygdala in Conscious Rats
Authors: Gören M.Z. , Akιcι A. , Berkman K. , Onat F.
Published: April 2003

The nuclei of hypothalamus and amygdala have been shown to be involved in the central cardiovascular homeostasis. Recent studies suggest that glutamate-containing neurons have an important role in the regulation of the central cardiovascular function. In this study, we demonstrate the roles of the central nucleus of the amygdala and the paraventricular nucleus of the amygdala and the paraventricular nucleus or the dorsomedial nucleus of the hypothalamus in N-methyl-D-aspartate (NMDA) induced blood pressure and heart rate changes in conscious Sprague-Dawley rats. Intracerebroventricular or parenchymal injections of NMDA evoke increases in arterial pressure. The NMDA-induced elevations in blood pressure are more prominent when NMDA is administered into the dorsomedial nucleus of the hypothalamus. Microinjections of NMDA into the dorsomedial hypothalamus exert significant heart rate increases, whereas NMDA when administered into the paraventricular nucleus of the hypothalamus or into the central nucleus of the amygdala has no significant effect on the heart rate. The dorsomedial nucleus of the hypothalamus is found to be the most effective site in this respect. The present study provides strong evidence for the tonic glutamatergic influence on blood pressure and heart rate via NMDA receptors located within the dorsomedial nucleus and to a lesser extent via those located within the paraventricular nucleus of the hypothalamus.
Searching for an Explanation for Diphthong Perception: Dynamic Tones and Dynamic Spectral Profiles
Authors: Schouten M.E.H. , Peeters W.J.M.
Published: April 2003

The aim was to find a psychophysical explanation for the perception, by naive listeners, of diphthongs as single vowels, even though they are essentially formant movements. Subjects were asked to match sinusoidal tone and resonance glides around 1,000 Hz with two connected steady-state tones or resonances whose frequencies could be controlled independently. The expectation was that short glides (below 120 ms) would give rise to single perceptual events without any movement in a particular direction, so that the two matching steady-state patterns would not show any frequency direction either; long resonance glides (above 120 ms), on the other hand, were expected to be perceived as rising or falling and matched accordingly. The results showed an effect of duration, although it interacted with glide width. At durations shorter than about 120 ms, subjects placed the two steady profiles with which they had to match the dynamic profile closer together than with durations over 120 ms; however, this only occurred if a glide covered more than 500 Hz, and is therefore irrelevant to diphthong perception.
Functional Deterioration following Placode Untethering in Myelomeningocele
Authors: Cochrane D.D. , Rassekh S.R. , Thiessen P.N.
Published: April 2003

Placode untethering in myelomeningocele patients can result in improvement and/or stabilization of neurological function, spinal curvature and pain. This paper reviews the outcome of untethering procedures in 24 patients to determine the frequency of subsequent functional deterioration. Decreased range of movement, joint stiffness and changes in muscle tone were the commonest indications for surgical intervention, occurring in 15 patients. Untethering resulted in improvement in 8 patients, stabilization of progression in 6 and continued deterioration in 1 patient. Two patients previously untroubled with spasticity became symptomatic within 3 months of the procedure. Changes in ambulation were present preoperatively in 9 patients. Stabilization was observed in 4 and improvement in 5. One of the patients, who had improved, deteriorated during the 1st year of follow-up. Alterations in bladder capacity and continence occurred in 7 patients. Improvement was seen in 2 patients, deterioration in 2 and no change in 3. Of the patients who improved, 1 subsequently deteriorated again within the 2nd postoperative year. Of those patients who had stable bladder function preoperatively, 6 subsequently deteriorated despite untethering. Pain was a less frequent symptom, occurring in 6 patients. Six patients became pain-free within 3 months of untethering. Two patients who did not have pain preoperatively had pain at the operative site persisting for up to 3 months postoperatively. Of the 20 patients having a single untethering procedure to date, 11 have further symptoms that can be attributed to retethering.
Endoscopic Third Ventriculocisternostomy: MR Assessment of Patency with 2-D Cine Phase-Contrast versus T2-Weighted Fast Spin Echo Technique
Authors: Fischbein N.J. , Ciricillo S.F. , Barr R.M. , McDermott M. , Edwards M.S.B. , Geary S. , Barkovich A.J.
Published: April 2003

Purpose: To determine if fast spin-echo T2 (FSE) is of equal value to flow-sensitive 2D cine phase-contrast (CPC) to assess patency of endoscopic third ventriculocisternostomies (VC). Patients and Methods: We reviewed clinical charts and MR scans of 27 patients who underwent third VC for treatment of obstructive hydrocephalus. Thirty-nine postoperative scans included both sequences and were assessed for the presence or absence of flow-related signal changes. Results: In 28 cases, FSE, CPC, and clinical findings suggested patency. In 1 case, CPC and FSE suggested occlusion, which was confirmed clinically and operatively. In the remaining cases, FSE showed better clinical correlation than did CPC. Conclusion: The assessment of third VC patency with FSE, a sequence available on most clinical scanners without a requirement for special hardware and software, is at least as sensitive in the qualitative assessment of VC function as CPC.
Lytic Skull Metastasis from a Follicular Thyroid Carcinoma in a Child
Authors: Kim Stanley H. , Kosnik Edward , Madden Christopher , Morran Stacy , Rusin Jerome , Gordon Timothy , Boue Daniel
Published: April 2003

We present a case of solitary lytic skull metastasis from a follicular thyroid carcinoma in a child. Salient clinical features, radiological findings, and histological distinctions of the metastatic skull tumor are described. Excision of the skull tumor followed by total thyroidectomy and 131I-radioablation therapy has resulted in good short-term outcome. This is the first published report of a metastatic skull lesion from a follicular thyroid carcinoma in a child. Such a malignant lesion can radiologically mimic a benign skull tumor and should be considered in the differential diagnosis of a solitary lytic skull lesion with a sclerotic margin.
The Role of Chemotherapy inNewly Diagnosed Ependymoma of Childhood
Authors: Souweidane Mark M. , Bouffet Eric , Finlay Jonathan
Published: April 2003

The use of chemotherapy in treating children with newly diagnosed ependymoma is currently being investigated, both clinically and experimentally. Assessment of the true efficacy of this modality is hampered by a lack of prospective randomized trials comparing conventional treatment schemes of aggressive surgical excision followed by radiation therapy with or without addition of chemotherapy. Although with current regimens, the role of chemotherapy in newly diagnosed disease appears limited, measurable disease responses have been recognized. Preliminary studies support the potential use of chemotherapy in infants in an effort to delay radiation therapy or even avoid radiation therapy, although with conventional chemotherapy, a delay exceeding 12 months is inadvisable. Additionally, preliminary data suggest that in children with incompletely resected tumors, chemotherapy may be of benefit as an adjunct to second-look surgery. Experimental work investigating chemotherapeutic sensitivity, molecular genetics, or mechanisms to overcome drug resistance may offer some benefit in utilizing chemotherapy for ependymoma of childhood.
Suprasellar Germinoma Associated with Cushing’s Disease and Diabetes insipidus in a Child
Authors: Coufal F. , Linarelli L. , James H.E. , Krous Henry
Published: April 2003

Cushing’s disease is described in a child with a suprasellar germinoma. The patient presented with all of the classic stigmata of Cushing’s disease as well as diabetes insipidus, but after surgical resection of the lesion was found to have pathology incompatible with an ACTH-secreting tumor. We believe that this is the first reported incidence of Cushing’s disease associated with a suprasellar germinoma. The implications of this unusual association are discussed.
Treatment of Intracranial Ependymoma by Surgery Alone
Authors: Hukin Juliette , Epstein Fred , Lefton Dan , Allen Jeffrey
Published: April 2003

Objective: This study aimed to determine the safety of deferring radiotherapy in pediatric intracranial ependymoma following a radiographically confirmed gross total resection in patients with localized disease. Methods: Children over age 3 were recruited prospectively from 1990 to 1997, following a surgical impression and radiologic confirmation of a gross total resection of an intracranial ependymoma. Results: 10/32 cases of intracranial ependymomas were both eligible and gave consent. 7 remain free of disease without further intervention. 3 recurred, 2 were salvaged with surgery and radiotherapy, none died. Conclusions: Deferral of radiotherapy following gross total resection alone is a safe option in supratentorial ependymomas. The pattern of recurrence is usually local and patients may be salvaged with additional surgery with or without radiotherapy.
Chiari III Malformation Treated with CSF Diversion and Delayed Surgical Closure
Authors: Snyder Jr. William E. , Luerssen Thomas G. , Boaz Joel C. , Kalsbeck John E.
Published: April 2003

Chiari III malformations are extremely rare hindbrain malformations that are associated with a high early mortality rate, or severe neurologic deficits in the survivors. The preferred treatment is early operative closure and CSF shunting. We report a case of a newborn infant with a Chiari III malformation with displacement of the brainstem and cerebellum into the cervical encephalocele which precluded immediate operative closure of the defect. Instead, a ventriculoperitoneal shunt was placed and the patient was followed with serial imaging studies. The child survived. The shunt allowed the brainstem and cerebellum to regress into the cervical spinal canal as the dilated cerebral aqueduct and fourth ventricle decompressed. A delayed closure of the cervical encephalocele was performed at 30 months of age. Cerebrospinal fluid diversion with delayed closure may be an option for large lesions.
Primary Ki-1-Positive T-Cell Lymphoma of the Brain in a Child
Authors: Buxton N. , Punt J. , Hewitt M.
Published: April 2003

A unique case of a female child with primary Ki-1-positive T-cell lymphoma of the brain is reported. Her clinical course is discussed and the previous literature is reviewed.
Toward a Simpler Surgical Management of Chiari I Malformation in a Pediatric Population
Authors: Krieger Mark D. , McComb J. Gordon , Levy Michael L.
Published: April 2003

A wide variety of surgical adjuvants to the standard bony decompression have been advocated in the treatment of the Chiari I malformation, especially when the tonsillar herniation is associated with hydrosyringomyelia. These include various shunting procedures, duroplasty, obex plugging, and resection of the cerebellar tonsils. Our practice has been to avoid these adjuvants and to perform a simple limited occipital craniectomy, C1 laminectomy, and dural opening. The dura mater is left open and overlain with oxidized cellulose. To evaluate the efficacy of this more limited procedure, a retrospective review was performed of the medical records of 31 consecutive patients treated over a 6-year period. Twenty-six (84%) of these patients had an associated spinal cord syrinx; all underwent the same procedure. The follow-up period ranged from 15 to 93 months, with all patients having at least one postoperative magnetic resonance imaging at 6 months. Twenty-three of the 26 patients (88%) who presented with a syrinx had significant resolution of the syrinx on follow-up scans with concomitant improvement of presenting signs and symptoms. Of the remaining 3 patients, 1 had progressive hydrocephalus and received a ventriculoperitoneal shunt, with symptom resolution. In the other 2 patients the syrinx did not diminish; both received syringopleural shunts. Postoperative morbidity includes a 26% incidence of headaches, of which half resolved within 5 days, and only 1 persisted beyond 2 weeks. Nausea and vomiting occurred in 16%. Neither of these figures significantly exceeds those of other large surgical series in which the dura mater was closed with a patch graft. Three patients (10%) did have a postoperative cerebrospinal fluid leak; all responded to bedside suturing without further sequelae. This study indicates that a simple bone removal and open dural decompression of the cervicomedullary junction is a safe, effective operative treatment for Chiari I malformation in children. Shunts, duroplasty, obex plugging, and tonsillar resection offer no benefit regarding the outcome when our series is compared to others in which such adjuvants were used.
A Prospective Analysis of the Use of Octylcyanoacrylate Tissue Adhesive for Wound Closure in Pediatric Neurosurgery
Authors: Wang Michael Y. , Levy Michael L. , Mittler Mark A. , Liu Charles Y. , Johnston Susan , McComb J. Gordon
Published: April 2003

Objective: Cyanoacrylate monomers have been developed for use as skin adhesives. Previous studies have demonstrated that using this skin adhesive for the closure of traumatic lacerations results in excellent cosmesis, decreased procedure-related pain and timesavings. Surgical Technique: Octylcyanoacrylate skin adhesive is applied after the placement of deep fascial sutures with close approximation of the skin edges. The adhesive is applied in liquid form and polymerizes rapidly to solid form. Multiple layers are applied forming a hard impenetrable barrier. Results: This technique was prospectively evaluated in the closure of 102 elective neurosurgical operations with 142 incisions: ventriculoperitoneal shunt insertion/revision (53%) and craniotomy for tumors (10%) were the commonest procedures. There were a total of 83 scalp, 36 abdominal, 8 neck, 6 chest and 6 lumbar incisions. The mean incision length was 5.1 cm (range 0.25–50 cm). Fifty-nine percent of the wounds had previous areas of operative incisions. Complications included 1 poor cosmetic result and 4 cerebrospinal fluid (CSF) leaks. Of the 4 patients with CSF leaks, 2 required operative wound revision, and 1 required ventriculoperitoneal shunting for hydrocephalus. Conclusion: Cyanoacrylate skin adhesive is a viable means of obtaining cosmetic wound closure. Its use requires attention to proper skin approximation and hemostasis. In our experience, propensity for CSF leakage especially in reoperative procedures is a relative contraindication.
Cervical Cord Tethering Mimicking Focal Muscular Atrophy
Authors: Kuo Meng-Fai , Wang Huei-Shyong , Yang Chi-Chao , Chang Yih-Leong
Published: April 2003

Spinal cord tethering rarely occurs in the cervical region. In adults, it usually results from previous operations. However, congenital origin is always diagnosed and treated early in the infant period. We report a 12-year-old boy with cervical spinal dysraphism which was erroneously diagnosed as focal muscular atrophy, a benign form of motor neuron disease. The patient was brought to our hospital because of rapid deterioration of symptoms. Careful evaluation disclosed a hairy dimple at the nuchal area, which led to the correct diagnosis. X-ray of the cervical spine showed spina bifida from C4 to C6 levels and fusion of the laminae of C4 and C5. Spine MRI studies disclosed that the cervical cord was tethered caudally and dorsally, and the ventral nerve roots were markedly stretched, especially over the left side. Surgical intervention was undertaken and the patient’s muscle power improved after untethering. The purpose of this report is to acquaint the reader with a surgically treatable condition that may appear to be benign focal amyotrophy. Skin lesion at the nuchal area should be carefully looked for.
Failure of Open Third Ventriculostomy for Shunt Infections in Infants
Authors: Akdemir Hidayet , Kurtsoy Ali , Öktem İ. Suat , Menkü Ahmet , Koç R. Kemal , Tucer Bülent
Published: April 2003

Open third ventriculostomy (OTV) was performed on 4 infants with noncommunicating hydrocephalus and intractable shunt infections. All patients were resistant or relapsed after treatment with intravenous and intraventricular antibiotics along with change of the shunt apparatus. We performed phase-contrast cine magnetic resonance imaging (MRI) for preoperative and postoperative evaluation of cerebrospinal fluid (CSF) flow at the aqueduct of Sylvius. All patients required a second OTV approximately 3 weeks after the first OTV due to closure of the patency. Our experience led us to view OTV as an unsuccessful procedure in infantile noncommunicating hydrocephalus due to an insufficiently developed subarachnoid space. The patients’ data, operative findings and probable causes of failure are presented here.
Cushing’s Disease in a 7-Month-Old Girl due to a Tumor Producing Adrenocorticotropic Hormone and Thyreotropin-Secreting Hormone
Authors: List J.V. , Sobottka S. , Huebner A. , Bonk C. , Koy J. , Pinzer T. , Schackert G.
Published: April 2003

We present the case of a 7-month-old baby with Cushing's disease due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma combined with cells producing thyreotropin-secreting hormone (TSH). In MRI scans, a contrast-enhancing lesion was seen inside the pituitary fossa, and it extended into the suprasellar region. On the assumption of a pituitary adenoma, surgery was performed. Corresponding with biochemical findings, histopathological evaluation revealed an ACTH- and TSH-producing tumor. Genetic analysis did not demonstrate an alteration at codon 201 (Arg) and 227 (Glu). To our knowledge, this is the first case described in a child of this age.
An Unusual Case of Dorsally Situated Bony Spur in a Lumbar Split Cord Malformation
Authors: Chandra P. Sarat , Kamal Raj , Mahapatra A.K.
Published: April 2003

A case of lumbar split cord malformation (SCM) with a bony spur situated dorsally is presented. This was associated with a hypertrophied posterior arch. The ventral dura was totally intact, and there was no fibrous septum connecting the bony arch to the dura. To our knowledge, such a case has not been reported earlier. In view of this unique finding, we propose a slight modification in Pang's unified theory of embryogenesis in the development of SCM.
Endoscopic Approach to Noncommunicating Fluid Spaces in the Shunted Patient
Authors: Yamini Bakhtiar , Goumnerova Lilliana C. , Frim David M.
Published: April 2003

Introduction: It is well known that shunted hydrocephalic patients can, over time, develop entrapped ventricles or cystic spaces not in communication with the remaining ventricles. This situation has traditionally been treated with placement of an additional catheter or shunt system in the noncommunicating fluid space. With the advent of minimally invasive endoscopic techniques, it has become possible to fenestrate trapped fluid spaces into the shunted ventricular system, thus preventing the need for additional catheters. Methods: Fifteen shunted patients presented with noncommunicating fluid spaces over a 4-year period at our two institutions. We attempted fenestration procedures in 14 of those patients. The various procedures included: septum pellucidum fenestration, cyst fenestration, third ventriculocisternostomy and a combination of the above. Results: Thirteen of 16 (81%) endoscopic fenestrations successfully prevented the need for a complicated shunting system. There were 3 technical failures (3/16, 19%) in which an additional catheter was added to the existing shunt system at the time of the endoscopic procedure. There were no adverse neurologic effects from the endoscopic procedures; however, in 4 of the 14 patients (29%) a shunt revision was performed between 2 and 30 days following the fenestration. Conclusions: These results show that the endoscopic approach to establishing communication between noncommunicating CSF spaces in the shunted patient is safe and efficacious in preventing the need for additional CSF catheters. Though we encountered failures, the majority of cases are technically feasible. In these patients early shunt malfunction may occur, most likely due to intraoperative bleeding and will require shunt revision.
Spina bifida in Saudi Arabia: Is Consanguinity among the Parents a Risk Factor?
Authors: Murshid Waleed R.
Published: April 2003

Introduction: Spina bifida is an important birth defect. Its incidence differs from one country to another due to different factors. The aims of this study were: (1) to estimate the incidence of spina bifida in Al-Madinah Al-Munawarah and compare it with the Eastern part of the Kingdom, and (2) to find out if consanguinity is a risk factor. Methodology: A prospective study was conducted over the period from April 1996 to March 1997 in the city of Al-Madinah Al-Munawarah, Western Province, Saudi Arabia. New cases of spina bifida were studied and compared to a control group of 72 cases. Results: During the study period, 18 cases of spina bifida were detected. The incidence was 1.09 per 1,000 live births. The male to female ratio was 2:1; however, this was not statistically significant. Consanguinity of the parents was found in 89% of the spina bifida parents and only 67% of the controls (p < 0.0005). Conclusion: (1) The incidence of spina bifida in the city of Al-Madinah Al-Munawarah was similar to that reported from the Eastern Province of Saudi Arabia. (2) The consanguinity of the parents was a significant risk factor.
Endovascular Treatment of Huge Cervicofacial Hemangioma Complicated by Kasabach-Merritt Syndrome
Authors: Komiyama Masaki , Nakajima Hideki , Kitano Shouhei , Sakamoto Hiroaki , Kurimasa Hiroko , Ozaki Hajime
Published: April 2003

A 2-month-old girl with a huge cervicofacial hemangioma complicated by Kasabach-Merritt syndrome was presented. Two weeks corticosteroid treatment was ineffective, and deterioration of coagulation parameters and compromise of the airway and left vision due to huge hemangioma prompted use of endovascular treatment. Transfemoral arterial embolization using polyvinyl alcohol particles resulted in rapid clinical improvement. Endovascular treatment should be considered as an important therapeutic option for hemangioma complicated by Kasabach-Merritt syndrome.