bluuebunny/crossref_metadata_2025 huggingface dataset:
Radical Surgery in a Neonate with Craniopharyngioma
Authors: Müller-Scholden Joachim , Lehrnbecher Thomas , Müller Hermann L. , Bensch Jürgen , Hengen Ralph H. , Sörensen Niels , Stockhausen Hans-Burckhard von
Published: April 2003

Ultrasonography revealed a suprasellar tumor in a fetus at 28 weeks of gestation. The male newborn, delivered 10 weeks later, was operated at the age of 17 days, and a craniopharyngioma was completely removed. Intraoperatively, inappropriate secretion of antidiuretic hormone occurred and was followed by diabetes insipidus causing imbalance of fluid and electrolytes. The tumor recurred and was totally removed 1 year later. Further development was uneventful and, at the age of 8 years, the boy is in generally good mental and physical condition except for a left-sided hemiparesis. In contrast to the poor outcome of neonatal craniopharyngioma reviewed in the literature, this case may encourage radical surgery even in the very young.
Bioresorbable Fixation for Congenital Pediatric Craniofacial Surgery: A 2-Year Follow-Up
Authors: Kurpad Shekar N. , Goldstein Jeffrey A. , Cohen Alan R.
Published: April 2003

We describe our experience with the use of a polymeric biodegradable system for the correction of congenital pediatric craniofacial malformations. These fixation methods present several advantages over conventional metallic fixation systems. Our series consists of 51 patients that underwent craniofacial surgery, 46 for craniosysostosis, and 5 for encephalocele. The mean age of the patients was 3 years (median age 9 months). Patients with coronal or metopic craniosynostosis underwent a bifrontal craniotomy and anterior cranial vault and orbital reconstruction. Three patients with late sagittal synostosis underwent cranial vault reconstruction in two stages. Encephalocele defects were repaired with osteotomies, and/or onlay bone graft. Lactosorb (Lorenz Biomet, Warsaw, Ind.) plates (cut from a prefabricated mesh) and screws were employed using established fixation techniques. Cranial bone was the source of all bone graft when required. Pre- and postoperative clinical, radiographic and photographic examinations were performed on all patients. At 2 years follow-up, no evidence of infection, erythema, extrusion, instability of the bony fragments or relapse has been noted. The plates themselves were universally impalpable by the one year follow-up examination. The results in this series support the use of resorbable fixation systems in the correction of congenital craniofacial deformities.
Surgical Treatment of Hypothalamic Hamartoma and Refractory Seizures
Authors: Kramer Uri , Spector Sergey , Nasser Walid , Siomin Vitali , Fried Itzhak , Constantini Shlomi
Published: April 2003

Refractory gelastic seizures are often associated with hypothalamic hamartoma (HH). Presurgical evaluation in such children often points to a distinct cortical region as the source of the seizures. A case of a child with HH and refractory seizures is presented. Video-EEG monitoring revealed a well-defined epileptic focus in the left frontal region. In accordance with the current understanding of the nature of hamartoma-related seizures, the hamartoma was resected. Follow-up evaluations revealed a marked improvement in seizure frequency and global functioning.
Intracranial Hemorrhage in Neonates with Unrecognized Hemophilia A: A Persisting Problem
Authors: Myles Lynn M. , Massicotte Patricia , Drake James
Published: April 2003

Hemophilia is a rare disorder, and an uncommon cause of intracranial hemorrhage in neonates. We present 2 patients with hemophilia A, who presented with massive subdural hemorrhages on day 5 and day 4 postpartum. Both were taken urgently to surgery without a diagnosis of hemophilia being established. Neither patient had a family history of hemophilia, and both were born following difficult deliveries. The activated partial thromboplastin time (APTT) was normal in patient No. 1 (subsequent factor VIII level 10%). In patient No. 2, the APTT was slightly prolonged, but initially interpreted as being within the normal range for age (subsequent factor VII level of <1%). Patient 1 rebled, required a second operation, and had a poor outcome. Patient 2 was given prophylactic fresh frozen plasma, and made a good recovery. Factor VIII assay should be performed in all term male babies presenting with intracranial hemorrhage. In urgent circumstances, prophylactic clotting therapy should be administered during surgery to prevent postoperative bleeding in an undiagnosed hemophiliac.
Brainstem Gliomas
Authors: Farmer Jean-Pierre , Montes José Luis , Freeman Carolyn R. , Meagher-Villemure Kathleen , Bond Mason C. , O’Gorman Augustin M.
Published: April 2003

Case records of 37 patients with a diagnosis of brainstem glioma treated at the Montreal Children’s Hospital from June 1989 to June 1999 were reviewed. 15 patients had diffuse pontine gliomas and 22 patients had focal forms of brainstem gliomas. The two groups were compared with respect to age, clinical evolution, radiological appearance, type of surgery practised, histological diagnosis, adjuvant treatments and survival. A non-pontine brainstem location, a cystic or exophytic component, bright enhancement with gadolinium injection, a histological diagnosis of pilocytic astrocytoma or ganglioglioma were favourable prognostic factors. Progression-free survival and overall survival were significantly worse in the group of patients with diffuse pontine gliomas. The relative impact of radical surgery and/or radiotherapy is analysed. Surgery coupled to adjuncts such as navigation, ultrasound and monitoring plays an important role for focal brainstem lesions. Focal/conformal radiotherapy has an adjuvant role but better treatments are needed for the diffuse pontine brainstem lesions.
Obstructive Hydrocephalus following Herpes simplex Virus Type 1 Encephalitis Treated by Repeated Third Ventriculostomy
Authors: Tyagi Atul , Chumas Paul , Ferrie Colin
Published: April 2003

A rare case of obstructive hydrocephalus due to aqueductal obstruction following neonatal herpes simplex virus type 1 encephalitis is presented. The child was treated by third ventriculostomy and vesicles were seen on the floor of the third ventricle. The stoma closed on two occasions and required repeat third ventriculostomy, which was successful in maintaining the child shunt-free.
Screening for Ventricular Shunt Function in Children with Hydrocephalus Secondary to Meningomyelocele
Authors: Liptak Gregory S. , Bolander Heidi M. , Langworthy Kristen
Published: April 2003

Objective: To evaluate the current method of using computerized tomographic (CT) scans to screen for ventricular shunt failure in children who have hydrocephalus. Design: Retrospective review of 112 randomly selected charts. Patients: Children diagnosed with infantile hydrocephalus secondary to meningomyelocele, who were treated at the Andrew J. Kirch Developmental Services Center since 1978. Results: One hundred and twelve patients were monitored with CT scans for an average of 12.2 years. There was a total of 2,869 CT scans and an average of 2.1 CT scans per year. Shunt failure was diagnosed 76% of the time by symptoms, 15% by physical findings and 8% by routine CT scans. Sixteen patients had no shunt failure, whereas the remaining 96 had 255 shunt failures. Complications occurred during 30 of the 255 admissions. One child died due to complications directly related to shunt failure. No statistically significant correlations were found between the length of stay or complications and method of diagnosis. Conclusions: Although children in this study received frequent CT scans, 76% of the episodes of shunt failure were diagnosed because of symptoms. Children admitted to the hospital with symptomatic shunt failure did not have more complications or a longer stay than those diagnosed by routine CT scan. This study suggests that the use of routine CT scans to diagnose shunt failure while patients are asymptomatic does not lead to significantly better medical outcomes and is not cost-effective. However, before routine CT scans are eliminated, a prospective study needs to be conducted that examines outcomes such as cognitive and psychological functioning.
Oligodendroglial Ganglioglioma with Anaplastic Features Arising from the Thalamus
Authors: Johnson Mahlon D. , Jennings Mark T. , Toms Steven A.
Published: April 2003

Anaplastic gangliogliomas with an oligodendroglial component are exceedingly rare tumors of uncertain growth potential. We report a 17-year-old female with a massive ganglioglioma containing anaplastic oligodendroglioma apparently arising from the thalamus. Two weeks after partial resection, she was started on a regimen including escalated doses of topotecan in combination with a fixed-dosage intensification regimen of cisplatin, cyclophosphamide and vincristine with subsequent hyperfractionated external beam radiotherapy. She currently has stable disease.
Giant Ependymal Cyst of the Temporal Horn – An Unusual Presentation
Authors: Pawar Sanjay J. , Sharma Rewati Raman , Mahapatra Ashok K. , Dev Ebenezer J.
Published: April 2003

Primary benign cystic lesions in the brain are uncommon. However, extracerebral cysts like arachnoid cyst, epidermoid cyst and craniopharyngiomas are fairly common lesions. Also, colloid cyst in the third ventricle, dermoid cyst and endodermal cyst in the extracerebral location are not uncommon. On the contrary, intraventricular ependymal and choroidal cysts in the intraventricular location are infrequent. Surgical intervention is warranted in cysts, which produce a mass effect and raised intracranial pressure. We present an interesting case of a giant intraventricular ependymal cyst in the temporal horn in a 14-year-old boy, who presented with recent onset of headaches and epilepsy. He also had long-standing progressive proptosis of the left eye and left temporal bossing. Excision of this cystic lesion was curative. Interesting clinical and neuroimaging features are presented.
What Is the Ideal Initial Valve Pressure Setting in Neonates with Ventriculoperitoneal Shunts?
Authors: Korinth M.C. , Gilsbach J.M.
Published: April 2003

In order to determine the optimal valve pressure setting during the first weeks in neonates after implantation of programmable Hakim valves and to analyze the benefits and possible side effects of a new treatment protocol in this age group, we performed this prospective study. In 20 consecutive newborns less than 5 weeks of age with hydrocephalus due to various etiologies, a ventriculoperitoneal shunt with a programmable Hakim valve at an extremely low initial valve pressure setting of 30–40 mm H2O was implanted. This ‘overdrainage’ was maintained, monitored by regular clinical examination and transcranial ultrasonographic imaging, until the wound healing was uneventfully completed and the permanent valve pressure setting of 100–120 mm H2O was chosen. In this age group, which is prone to specific noninfectious shunt complications like wound breakdown, cerebrospinal fluid (CSF) fistula and subcutaneous CSF collections, none of these complications were seen, nor were there any persisting overdrainage phenomena on transcranial ultrasonography. Initial, temporary ‘overdrainage’ represents a simple, useful and risk-free therapy in neonates with programmable shunts which might lower the incidence of typical noninfectious complications in this age group.
Endoscopic Intraventricular Surgery for Treatment of Hydrocephalus and Loculated CSF Space in Children Less than One Year of Age
Authors: Fritsch Michael J. , Mehdorn Maximilian
Published: April 2003

Controversy exists regarding whether children under 1 year of age have a higher risk of treatment failure after neuroendoscopic procedures for the treatment of hydrocephalus than older children. We retrospectively reviewed the surgical management and clinical outcome of 15 infants who underwent neuroendoscopic surgery for the treatment of CSF space loculation and hydrocephalus. We performed 8 third ventriculostomies, 3 endoscopic arachnoid cyst fenestrations, 2 aqueductoplasties, 1 septostomy and in 1 patient, three endoscopic fenestrations for isolated ventricular compartments. Two of the third ventriculostomies, 1 of the aqueductoplasties and the 1 septostomy failed, and these patients underwent placement of a ventriculoperitoneal shunt. In all other patients, symptoms and signs related to hydrocephalus or CSF space loculation were relieved effectively after the endoscopic procedure. We conclude that neuroendoscopy presents an effective alternative for the treatment of hydrocephalus and CSF loculation in infants less than 1 year of age.
Cervical Subluxation after Surgery and Irradiation of Childhood Ependymoma
Authors: Fletcher Daniel T. , Warner William C. , Muhlbauer Michael S. , Merchant Thomas E.
Published: April 2003

Aggressive resection followed by postoperative radiation therapy directed at the tumor bed characterizes the treatment of childhood infratentorial ependymoma. Tumor resection often requires access to the upper portion of the cervical spinal canal, which places the patient at risk of complications, including destabilization. Two cases of cervical subluxation after surgery and irradiation for infratentorial ependymoma are presented and discussed to identify factors that may be responsible for this uncommon treatment complication. Cervical laminotomies, multiple surgeries, postoperative infection and the addition of radiation therapy may be contributory. Because second resection will be an important component of the next generation of cooperative group studies for infratentorial tumors, the incidence and severity of this treatment-related complication should be documented and efforts should be made to image the upper portion of the cervical spine during routine follow-up.
Reversal of Haemorrhagic Shock in Rats by Tetrahydroaminoacridine
Authors: Savci Vahide , Çavun Sinan , Gürün M. Sibel , Ulus Ismail H.
Published: April 2003

The cardiovascular effects of tetrahydroaminoacridine (tacrine; THA) were investigated in haemorrhaged rats. Intracerebroventricular (i.c.v.) injection of THA (10, 25 and 50 µg) restored blood pressure in a dose- and time-dependent manner. Atropine (10 µg, i.c.v.), a muscarinic receptor antagonist, attenuated the pressor response to THA (25 µg, i.c.v.), while mecamylamine (50 µg, i.c.v.), a nicotinic receptor antagonist, caused only a slight blockade in the pressor effect of THA. Simultaneous pretreatment with atropine and mecamylamine almost abolished the blood pressure effect of i.c.v. THA (25 µg). Haemorrhage increased plasma levels of adrenaline, noradrenaline, vasopressin and plasma renin activity. THA (25 µg, i.c.v.) administration caused additional increases in vasopressin and adrenaline levels but not of renin activity and noradrenaline levels. The reversal of hypotension by THA was greatly attenuated by administration of either prazosin, an α1-adrenoceptor antagonist (0.5 mg/kg, i.v.) or by the vasopressin V1 receptor antagonist [β-mercapto-β,β-cyclopenta-methylenepropionyl1, O-Me-Tyr2-Arg8]-vasopressin (10 µg/kg, i.v.). Pretreatment of rats with both prazosin and the vasopressin antagonist simultaneously completely inhibited the pressor response. Intravenous administration of THA (1, 1.5 and 3 mg/kg) also reversed hypotension in rats. Atropine (10 µg, i.c.v.) greatly attenuated the pressor response to THA (1.5 mg/kg, i.v.), while mecamylamine (50 µg, i.c.v.) failed to change the pressor effect of THA. In anaesthetised haemorrhaged rats, THA (1.5 mg/kg, i.v.) increased blood pressure and survival time of the animals. These results show that centrally and peripherally injected THA reverses haemorrhagic hypotension and increases survival time in rats. Activation of central muscarinic and nicotinic receptors is involved in the pressor response to i.c.v. THA. The pressor effect of i.v. THA is solely mediated by central muscarinic receptors. Moreover, the increase in plasma adrenaline and vasopressin levels appears to be involved in the pressor effect of THA.
Biochemical Activities of Trimetoquinol Analogs at Human β1- and β3-Adrenergic Receptors
Authors: Konkar Anish A. , Nikulin Victor I. , De Los Angeles Joseph , Hong Seoung-Soo , Fertel Richard H. , Miller Duane D. , Feller Dennis R.
Published: April 2003

The biochemical activities of trimetoquinol (TMQ) analogs were evaluated at the human β1- and β3-adrenergic receptor (AR) subtypes expressed in Chinese hamster ovary cells. In radioligand binding assays, the 1-benzyl iodine-substituted analogs exhibited higher binding affinities at both β1- and β3-AR subtype as compared to TMQ. In cAMP accumulation assays, these analogs exhibited high potencies at both β1- and β3-AR. The 3′,5′-diiodo-4′-amino analog of TMQ was the most potent β3-AR agonist, 17-fold more potent at the β3-AR versus the β1-AR. Masking of the 6,7-dihydroxy group of the catechol ring of 3′,5′-diiodo-4′-acetamido analog of TMQ, a potent β1- and β3-AR agonist, abolished activity at both β-AR subtypes. Furthermore, substitution of a strong electron withdrawing group such as the trifluoromethyl moiety at the 1-benzyl ring of TMQ dramatically decreased potency at β1- and β3-AR compared to TMQ. Replacement of the 1-benzyl ring of TMQ with a naphthalene ring did not alter affinity but reduced potency of resulting 1-naphthylmethyl and 2-naphthylmethyl analogs at β1- and β3-AR compared to TMQ. Our results define the structural and electronic properties of substituents on TMQ necessary for potent activation of β1- and β3-AR and suggest that further modifications of the 1-benzyl iodine-substituted analogs may yield potent β3-AR agonists.
Effect of KAD-1229, a Nonsulfonylurea Hypoglycemic Agent, on Plasma Glucose and Insulin in Streptozotocin-Induced Diabetic Dogs
Authors: Misawa Keiko , Ichikawa Kiyoshi , Ojima Kazuma , Hamano Shuichiro , Kitamura Tsuyoshi , Komatsu Hidetada
Published: April 2003

Hypoglycemic agents with a rapid onset and short duration of action should be useful for controlling postprandial hyperglycemia. Our aim was to establish a diabetes mellitus model in dogs, and then during an oral glucose tolerance test to compare the hypoglycemic effect and insulinotropic action of KAD-1229, a new hypoglycemic agent, with that of gliclazide, a conventional sulfonylurea. In this model, KAD-1229 reduced the increase in plasma glucose level without producing hypoglycemia. Gliclazide had a weaker effect on reduction of the glucose increase and caused hypoglycemia via a significantly raised insulin secretion in the late phase. A rapid insulinotropic action of KAD-1229 was clearly observed in the portal venous blood. The results suggest that in type 2 diabetes caused by, at least, insulin deficiency, KAD-1229 may improve impaired insulin secretion in the early phase and attenuate hyperglycemia without causing a sustained hypoglycemia.
Effects of 5-HT4 Receptor Agonist Prokinetic Agents on the Action Potential Parameters of Isolated Rabbit Myocardium
Authors: Noguchi Kazuo , Ito Chika , Isobe Yoshihiko , Fukushima Kiyomi , Tanaka Yoshio , Tanaka Hikaru , Shigenobu Koki
Published: April 2003

The effects of TS-951, a novel gastrointestinal prokinetic agent with 5-HT4 receptor agonistic action, on the action potential parameters of isolated rabbit Purkinje fiber, ventricular muscle and sinoatrial node, and on the spontaneously beating rates of isolated rabbit right atria were compared with those of cisapride. TS-951 had no effect on the action potential parameters in both rabbit Purkinje fiber and ventricular muscle preparations. However, cisapride significantly prolonged action potential duration (APD) in both preparations. Both TS-951 and cisapride produced a negative chronotropic effect in rabbit right atria; TS-951 and cisapride at 3 × 10–5 mol/l reduced the beating rate by about 20 and 40%, respectively. In the sinoatrial node preparations, TS-951 (3 × 10–5 mol/l) as well as cisapride (10–6 mol/l) prolonged cycle length and APD and reduced the diastolic depolarization rate. These results indicate that TS-951 does not appear to possess electrophysiological features leading to cardiotoxicity such as QT prolongation and, thus, torsades de pointes in common with cisapride.
Adverse Effects of Intravenous Immunoglobulin Therapy in 56 Patients with Autoimmune Diseases
Authors: Sherer Yaniv , Levy Yair , Langevitz Pnina , Rauova Lubica , Fabrizzi Fabrizzio , Shoenfeld Yehuda
Published: April 2003

Objective: To test the adverse effects and viral safety of intravenous immunoglobulin (IVIg) use in autoimmune diseases. Methods: Fifty-six patients with various autoimmune diseases who were treated with one to six IVIg courses were evaluated for the presence of adverse effects following IVIg therapy and were screened before and after the treatment for the presence of serum human immunodeficiency virus antibodies, hepatitis C virus antibodies, and hepatitis B surface antigen. Results: Among the 56 patients, 20 (36%) had at least one adverse effect following at least one of the treatment courses. These included headache, low-grade fever, chills, anemia, low-back pain, transient hypotension, nausea, intensified perspiration, and superficial and deep vein thromboses. Whereas the presence of adverse effect to IVIg was unrelated to either the clinical response to the treatment or to the nature of the autoimmune disease, the occurrence of an adverse effect in the first treatment course was significantly associated with a greater chance for an adverse effect in the subsequent courses. No transmission of any of the three viral agents examined could be detected. Conclusions:  Although IVIg use in autoimmune diseases is associated with adverse effects in about one third of the patients, these effects are usually mild and transient. Patients who develop adverse effects during the first treatment course may be at increased risk of adverse effects during the subsequent IVIg courses.
Pharmacological Properties of Fidarestat, a Potent Aldose Reductase Inhibitor, Clarified by Using Sorbitol in Human and Rat Erythrocytes
Authors: Sobajima Hiroshi , Aoki Takahiko , Sassa Hiromi , Suzuki Takeshi , Taniko Kaori , Makino Mitsuhiro , Mizuno Kuniharu , Suzuki Tsunemasa
Published: April 2003

We examined the effect of fidarestat on the increase in sorbitol content in erythrocytes from healthy volunteers in vitro. Fidarestat inhibited the increase with an IC50 value of 18 nmol/l. A subsequent experiment showed that fidarestat had a similar inhibitory effect on the increase in sorbitol content in erythrocytes from diabetic patients. On the other hand, epalrestat, the only aldose reductase inhibitor used clinically, inhibited increase in sorbitol content at a concentration over 500-fold higher than fidarestat. Although the IC50 value of fidarestat was not affected by fasting plasma glucose, HbA1C, age, aldose reductase content or gender, there was a significant positive relationship between the IC50 value of epalrestat and fasting plasma glucose. In addition, in fidarestat (0.25–2 mg/kg)-treated diabetic rats, the inhibitory rate for erythrocyte sorbitol accumulation was well correlated with that for nerve sorbitol accumulation, which indicates that erythrocyte sorbitol is available for assessing the state of sorbitol pathway flux in target tissue after fidarestat administration. These results suggest that fidarestat potently inhibits the increase in sorbitol pathway flux in diabetic patients independent of various factors and that erythrocyte sorbitol is useful for its estimation.
Bufuralol Metabolism by Guinea Pig Adrenal and Hepatic Microsomes
Authors: Colby Howard D. , Nowak Deanne M. , Longhurst Penelope A. , Zhang Xiaoshi , Hayes Jill R. , Voigt Jeffrey M.
Published: April 2003

Previous investigations demonstrated that CYP2D16 was expressed at high levels in guinea pig adrenal microsomes. The studies presented here were done to determine whether adrenal metabolism of bufuralol (BUF), a model CYP2D substrate, was similar to that in the liver. Guinea pig adrenal microsomes converted BUF to 1′-hydroxybufuralol (1′-OH-BUF) as the major metabolite and smaller amounts of a compound identified as 6-hydroxybufuralol (6-OH-BUF). In contrast, 6-OH-BUF was the major product formed by hepatic microsomal preparations. The apparent Km values were similar for 1′-OH-BUF and 6-OH-BUF production in each tissue. Quinidine, a selective CYP2D inhibitor, decreased the production of both BUF metabolites equally in liver and adrenal microsomes. Cortisol also caused equivalent decreases in the rates of 1′-OH-BUF and 6-OH-BUF formation by adrenal microsomes, but had no effect on hepatic BUF metabolism. Although both BUF metabolites may be produced by CYP2D16, unknown factors appear to effect some differences in the catalytic characteristics of BUF metabolism in adrenal and liver. The large amount of 6-OH-BUF produced distinguishes BUF metabolism in guinea pigs from that in other species previously studied.
Parathyroid Hormone-1 Receptor Down-Regulation in Kidneys from Rats with Chronic Renal Failure
Authors: Edwards Richard M. , Contino Lisa C. , Gellai Miklos , Brooks David P.
Published: April 2003

Although secondary hyperparathyroidism is a common complication of chronic renal failure, few studies have examined the characteristics of parathyroid hormone (PTH) binding to the kidney or the regulation of the PTH receptor in chronic renal disease. In this study we measured PTH binding to the PTH-1 receptor in renal cortical membranes from normal rats and from rats with experimentally induced chronic renal failure. In normal rats, analysis of saturation binding experiments using 125I PTH-related peptide (chicken, cPTHrP) revealed apparent Kd and Bmax values of 1.16 ± 0.14 nmol/l and 338 ± 22.7 fmol/mg, respectively. Three weeks following induction of renal failure there was no change in the affinity of the PTH-1 receptor (Kd = 1.51 ± 0.24 nmol/l) but the Bmax was reduced by 45% (183 ± 32.5). In normal rats which had undergone thyroparathyroidectomy, the Kd was unchanged (1.17 ± 0.09) while the Bmax increased to 459 ± 31 fmol/mg. We conclude that chronic renal failure is accompanied by a downregulation of renal PTH-1 receptors.
Distribution of P2X1 and P2X3 Receptors in the Rat and Human Urinary Bladder
Authors: Elneil Sohier , Skepper Jeremy N. , Kidd Emma J. , Williamson John G. , Ferguson Douglas R.
Published: April 2003

Adenosine 5′-triphosphate (ATP) is known to play a significant role as a neurotransmitter in smooth muscle. There is evidence to show that ATP can cause bladder contractions and may also be involved in the processing of sensory information in the urinary bladder. These effects are likely to be mediated by P2X receptors, namely P2X1 and P2X3, respectively. This study set out to investigate their distribution in rat and human urinary bladders. P2X1 receptor immunoreactivity was found on detrusor muscle fibres and P2X3 receptor immunoreactivity was found in the urothelium of both species. This is the first demonstration of a non-neuronal localisation for P2X3 receptors. No clear evidence was found for the presence of P2X3 receptors on calcitonin gene-related peptide-containing sensory nerves and therefore P2X3 receptors may not have a direct role in the mediation of sensory responses to ATP in the urinary bladder.
Effects of Nicorandil Administration on Survival Rate and Arrhythmias during Reperfusion in Anesthetized Rabbits
Authors: Das Biswadeep , Sarkar Chayna , Karanth K. Sudhakar
Published: April 2003

The aim was to study the effects of nicorandil (an ATP-sensitive K+ channel opener) and tolbutamide (an ATP-sensitive K+ channel blocker) on reperfusion-induced arrhythmias in pentobarbitone and ketamine anesthetized rabbits. Arrhythmias were induced by reperfusion for 20 min following a 15-min ligation of the left main coronary artery with a silk ligature. Rabbits were pretreated with nicorandil (0.47, 0.93 or 1.86 mg/kg i.v.) or tolbutamide (180 mg/kg i.p.) or vehicle (dimethylsulfoxide/saline) before the coronary artery occlusion. In the control group (n = 10), only 60% of the animals survived during reperfusion. Intravenous pretreatment with 0.47, 0.93 or 1.86 mg/kg of nicorandil increased the survival rate to 86% (n = 7), 75% (n = 8) and 86% (n = 7), respectively. Nicorandil pretreatment significantly decreased the incidence and duration of reperfusion-induced life-threatening arrhythmias and increased the number of animals that survived without developing any arrhythmia. Tolbutamide pretreatment was associated with a decreased survival rate of 50% (n = 12) and an increase in the incidence and duration of reperfusion-induced arrhythmias. Pretreatment with nicorandil may result in protection against reperfusion-induced arrhythmias and increased survival in anesthetized rabbits.
Increased Nitric Oxide Accounts for Decreased Basal Vascular Tone and Responsiveness in the Resistance Vessels of High-Cholesterol-Fed Rabbits
Authors: Fitch Richard , Da Cunha Valdeci , Kauser Katalin , Dole William , Parkinson John , Vergona Ronald , Sullivan Mark E. , Wang Yi-Xin
Published: April 2003

The objective of this study was to determine the effects of hypercholesterolemia on basal vascular tone and vascular responses to pharmacologic agents in hindquarter resistance vessels. Blood pressure and hindquarter blood flow were measured in conscious rabbits fed a high cholesterol diet (1%) for 17 weeks (HC) compared to age-matched rabbits fed a normal diet (control). Basal hindquarter blood flow and vascular conductance were significantly higher in HC than in control rabbits. Administration of a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (100 mg/kg) decreased basal hindquarter blood flow and vascular conductance in a greater magnitude in HC than in control rabbits, thus, abolished the differences in both the flow and conductance between 2 groups, indicating that increased NO was responsible for reduced basal vascular tone in the HC rabbits. L- (30 mg/kg), a selective inducible NOS (iNOS) inhibitor had no effects on either flow or conductance. This result does not support the involvement of iNOS. In separate experiments, animals were anesthetized and instrumented with an extracorporeal circuit to measure perfusion pressure under constant blood flow to the hindquarter vascular bed. In the HC group, vascular responses to acetylcholine, S-nitroso-N-acetyl-penicillamine and phenylephrine were all attenuated when compared to the responses in the control rabbits. These results indicate that local overproduction of NO due to hypercholesteremia could desensitize smooth muscle reactivity, thus causing general vascular hyporesponsiveness to vasoactive agents.
Effects of Diacerein on Indomethacin-Induced Gastric Ulceration
Authors: Tamura Tadafumi , Yokoyama Toshihide , Ohmori Kenji
Published: April 2003

We investigated the effect of diacerein, an antiosteoarthritic agent, and its metabolite, rhein, on the production of reactive oxygen species (ROS) from neutrophils as well as the protective effect of diacerein on indomethacin-induced gastric ulceration and its protection mechanism. Rhein inhibited the ROS production from N-formyl-methionyl-leucyl-phenylalanine or phorbol-12-myristate-13-acetate-activated human peripheral neutrophils. Indomethacin-induced gastric ulceration was significantly inhibited by oxygen radical scavengers and 16,16-dimethyl-prostaglandin E2 (dmPGE2) but not by allopurinol. Diacerein inhibited indomethacin-induced gastric ulceration in a dose-dependent manner. Diacerein did not affect the gastric mucosal PGE2 content. In addition, diacerein inhibited HCl + ethanol-induced gastric ulceration. These data indicate that the inhibitory effect of diacerein on indomethacin-induced gastric ulceration could be mediated not by the augmentation of gastric mucosal PGE2 production but by the suppression of ROS production based on its inhibition of neutrophil activation.
Effects of Chronic Administration of Sarpogrelate on Systolic Blood Pressure of Spontaneously Hypertensive Rats: Comparison with Quinapril
Authors: Setoguchi Yuki , Ohnuki Toshio , Rashid Mamunur , Nakamura Takashi , Hattori Kaoru , Nagatomo Takafumi , Watanabe Kenichi , Mitomi Akio , Nakazawa Mikio
Published: April 2003

Effects of long-term sarpogrelate (5-HT2 antagonist) administration on the systolic blood pressure of Wistar-Kyoto normotensive rats (WKYs) and spontaneously hypertensive rats (SHRs) were studied and compared with those of quinapril (ACE-I). Sarpogrelate and quinapril were administered orally for 12 weeks and body and heart weights, systolic blood pressure and the relationships between heart weight and systolic blood pressure were determined. Although both drug treatments caused decreases in the body weight of WKYs and SHRs, only quinapril induced a decrease in the heart weight of SHRs. In addition, quinapril induced a dose-dependent decrease in systolic blood pressure in WKYs and SHRs while sarpogrelate had no effect on systolic blood pressure. Thus, quinapril showed hemodynamic effects on WKYs and SHRs, but the 5-HT2 antagonists sarpogrelate did not shown such effects, suggesting that 5-HT2 receptor antagonists may not be important for controlling systolic blood pressure.
Effect of Hexasulfobutylated C60 on the Isolated Aortic Ring of Guinea Pig
Authors: Huang Shiang Suo , Mashino Tadahiko , Mochizuki Masataka , Chiang Long Y. , Chih Lan Hui , Hsieh Hung Ming , Teng Chen Ming , Okuda Kensuke , Hirota Takasi , Tsai Ming Cheng
Published: April 2003

The effects of hexasulfobutylated C60 (FC4S) and monomalonic acid C60 (MMA C60), the fullerene C60 derivatives, on isolated endothelium-containing or endothelium-denuded aorta of guinea pig were studied pharmacologically in vitro. In the endothelium-containing preparation of the aortic rings, phenylephrine (PHE) elicited contracture and acetylcholine (ACh) elicited a relaxing effect on the PHE-precontracted preparation. In the PHE-precontracted preparation, MMA C60 (10 µmol/l) did not elicit a relaxing effect on the PHE-precontracted preparation. However, MMA C60 (10 µmol/l) significantly reduced the maximum response of the relaxation elicited by ACh. FC4S itself significantly relaxed the PHE-precontracted aortic rings. ACh-induced relaxation in PHE-precontracted endothelium-containing strips of the aortic rings was significantly potentiated if pretreated with FC4S (10 µmol/l). In the denuded aortic rings, FC4S did not elicit the relaxing effect in the PHE-precontracted preparation. The relaxing effect of FC4S on the PHE-precontracted preparation was not altered when superoxide dismutase (250 units/ml) was pretreated. However, the relaxing effect was reduced when N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mmol/l) or methylene blue (1 µmol/l) was pretreated. These results demonstrated that the vasorelaxation effect of FC4S on the PHE-precontracted aortic ring is partly dependent on the release of nitric oxide (NO) or an NO-derived substance from the vascular endothelium.
Comparison of Furosemide and Vinblastine Secretion from Cell Lines Overexpressing Multidrug Resistance Protein (P-Glycoprotein) and Multidrug Resistance-Associated Proteins (MRP1 and MRP2)
Authors: Flanagan Shawn D. , Cummins Carolyn L. , Susanto Miki , Liu Xiaoli , Takahashi Lori H. , Benet Leslie Z.
Published: April 2003

Recent studies in our laboratory have shown that the loop diuretic, furosemide, is actively secreted by Caco-2 cells and rat jejunal tissue. This active secretion could be the result of efflux transporters such as P-gp, MRP1 or MRP2 (cMOAT). To determine if any of these transporters is responsible for the secretion of furosemide, we compared directional permeability in the wild-type cell lines, MDCK strains I and II, and LLC-PK1, vs. cell lines that overexpress a single transporter, in both the presence and absence of various inhibitors, for furosemide as compared to vinblastine. Sulfinpyrazone significantly inhibited the transport of vinblastine in MRP2 expressing cells, but not the wild-type controls. Vinblastine could not be confirmed as a substrate of MRP1. We were also unable to demonstrate that any particular transporter affected furosemide in excess of the background effects of endogenous transporters in the parental cell lines. Furosemide secretion from these kidney-derived cell lines is probably not the primary result of any of the well characterized efflux transporters (P-gp, MRP1 or MRP2), although they may still play a role in the observed Caco-2 secretion. This equivocal result acknowledges the difficulty in trying to determine the effect of a single protein in a complicated expression system.
Diminished Inibitory Action of Ethanol on the Contraction of Gallbladder Isolated from Chronically Ethanol-Fed Guinea Pigs
Authors: Masui Hidehisa , Wakabayashi Ichiro , Siogawa Kenichi , Koizumi Naoko
Published: April 2003

Ethanol is known to decrease the gallbladder contractility. The purpose of this study was to clarify the mechanism of tolerance to the inhibitory action of ethanol on the gallbladder contractility. Male guinea pigs were fed ethanol (3%) or calorie-matched sucrose in the drinking water for 4 weeks. Then, the gallbladder was isolated, and its isometric tension was measured. The contractile responses to KCl, BAY K8644, histamine, and phorbol 12,13-dibutyrate in the normal medium were not different between the gallbladder strips from ethanol-fed and control guinea pigs. Ethanol at 25 mmol/l in vitro did not affect the contractile responses to KCl and BAY K8644 in the gallbladder strips from both ethanol-fed and control guinea pigs. On the other hand, ethanol at 25 mmol/l in vitro significantly inhibited the contractile responses to histamine and phorbol 12,13-dibutyrate in the gallbladder strips from the control guinea pigs, but it did not affect the contractile response to histamine and significantly augmented that to phorbol 12,13-dibutyrate in the strips from the ethanol-fed guinea pigs. Diphenhydramine, a selective H1 receptor antagonist, abolished the histamine contraction in gallbladder strips from both control and ethanol-fed guinea pigs, while cimetidine, a selective H2 receptor antagonist, did not affect histamine contraction, implying that histamine-induced contraction of guinea pig gallbladders is mediated only by H1 receptors. Verapamil (1 µmol/l) completely inhibited the phorbol 12,13-dibutyrate-induced contraction of the strips from both ethanol-fed and control guinea pigs. The histamine-induced contraction was partly inhibited in the absence of Ca2+ in the medium. In the gallbladder strips from both ethanol-fed and control guinea pigs, ethanol at 25 mmol/ in vitro did not affect the histamine-induced contraction in the absence of extracellular Ca2+. Tolerance to the inhibitory action of ethanol developed selectively on contractile responses to histamine and phorbol 12,13-dibutyrate. Chronic ethanol administration produces tolerance to in vitro gallbladder contractility mediated by the Ca2+ entry through L-type Ca2+ channels linked with protein kinase C activation.
Distribution and Muscle-Sparing Effects of Clenbuterol in Hindlimb-Suspended Rats
Authors: von Deutsch Daniel A. , Abukhalaf Imad K. , Wineski Lawrence E. , Roper Rayan R. , Aboul-Enein Hassan Y. , Paulsen Douglas F. , Potter David E.
Published: April 2003

Based on their anabolic properties in skeletal muscles, β-adrenergic agonists are of interest as potential countermeasures to microgravity-induced skeletal muscle atrophy. The levels of clenbuterol (Cb), a β2-adrenergic agonist, in both plasma and skeletal muscle were higher in hindlimb-suspended rats than in their nonsuspended Cb-treated controls. Cb treatment was shown to help maintain the body weight in suspended rats, while reducing the amount of mesenteric fat. However, hindlimb suspension attenuated Cb’s lipolytic effects. In skeletal muscle, the magnitude of response to unloading and Cb treatment followed a general regional pattern and was muscle and type specific. The highest magnitude of response to unloading was in predominantly slow-twitch muscles, and the least responsive were the predominately fast-twitch muscles.
In vivo and in vitro Effects of Bromelain on PGE2 and SP Concentrations in the Inflammatory Exudate in Rats
Authors: Gaspani Leda , Limiroli Elena , Ferrario Paolo , Bianchi Mauro
Published: April 2003

The effects of bromelain were examined in rats with subcutaneous carrageenin-induced inflammation. After oral in vivo administration, bromelain (10 and 20 mg/kg p.o.) induced a significant decrease of both PGE2 and substance P concentrations in the exudate. When added to the inflammatory exudate in vitro, the drug (25, 50, 100 µg/ml) did not affect PGE2 concentrations and induced an increase in the substance P levels. Our data indicate that bromelain reduces the production of two key mediators of inflammation. This effect does not seem to be related to a direct action of the drug on PGE2 and SP released in the exudate in response to the inflammatory stimulus.
Effect of YM-44781, YM-44778 and YM-49598, Novel Tachykinin Antagonists, in a Drug-Induced Bladder Contraction Model
Authors: Choppin Agnes , Groke Gretchen , Bringas Analyn , Stepan George , Dillon Michael P.
Published: April 2003

The radioligand binding profiles and in vivo pharmacological characteristics of YM-44781, YM-44778 and YM-49598, novel non-peptide tachykinin receptor antagonists, were examined and compared to those of FK-888 and GR-159897. Since no functional NK3 receptors were found in the rat bladder, the emphasis will be on the other two subtypes. YM-44781 and YM-49598 exhibited high binding affinities at NK2 (pKi = 9.94 ± 0.03) and NK1 (pKi = 9.09 ± 0.02) receptors, respectively, whereas YM-44778 exhibited high binding affinities at both NK1 (pKi = 8.08 ± 0.07) and NK2 (pKi = 8.55 + 0.04) receptors stably transfected in CHO-K1 cells (Chinese hamster ovary cells). In an in vivo rat model, a drug-induced bladder contraction model, antagonism of the contractions produced by the selective NK2 receptor agonist, [βAla8]neurokinin A (4–10) (10 µg·kg–1 i.v.) was observed after intravenous administration (dose range 0.001–1 mg·kg–1) of YM-44781 and YM-44778 (IC50 = 27 ± 8 and 100 ± 44 µg· kg–1, respectively). YM-44781 was more potent (about 3-fold) than YM-44778. YM-49598 was almost inactive but produced a potent inhibition (IC50 = 11 ± 7 µg·kg–1) of the contraction of the rat urinary bladder induced by challenge with the NK1-selective receptor agonist [Sar9,Met(O2)11]substance P sulphone (0.3 µg·kg–1). YM-44781 and YM-44778 did not produce major inhibition of [Sar9,Met(O2)11]substance P-induced bladder contraction. These findings indicate that YM-44781 and YM-49598 are potent NK2 and NK1 receptor antagonists, respectively, whereas YM-44778 is a nonselective NK2/NK1 receptor antagonist in the drug-induced bladder contraction model.
Developmental Trends in Voice Onset Time: Some Evidence for Sex Differences
Authors: Whiteside S.P. , Marshall J.
Published: April 2003

This study reports on an investigation into the voice onset time (VOT) patterns of the plosives /p b t d/ in a group of 30 children aged 7 (n = 10), 9 (n = 10) and 11 (n = 10) years. Equal numbers of girls and boys participated in the study. Each child named a series of letter objects to elicit /p b t d/ in a syllable onset position with a fixed vowel context. VOT data were examined for age, sex and plosive differences with the following hypotheses: Firstly, that there would be sex differences in the VOT patterns of preadolescent children. Secondly, that the sex differences in VOT patterns would be linked to age and development, and that these would eventually become marked by the age of 11 years, by which time adult-like VOT values should have been achieved. Finally, that the extent of sex and age differences would be dependent upon the plosive being investigated. Results indicated patterns of decrease with age in the VOT values of /p b/ for the boys, with some evidence of increases in the VOT values of /t/ for the girls. In addition, ‘voiced’ and ‘voiceless’ cognates showed a more marked bimodal distribution in the girls‘ VOT patterns. This bimodal distribution was investigated by examining the degree of difference between the VOT values of voiced and voiceless cognate pairs /p b/ and /t d/, and examining the effects of age, sex and cognate pair. These results indicated that more marked sex differences in the ‘voiced’/‘voiceless’ contrast emerged between the data of the 9- and 11-year-olds, a pattern, which was more marked for the alveolar plosives. These preliminary results confirmed all three hypotheses. The findings are presented and discussed both within a developmental and sociophonetic framework.
Schizophrenics Show a Failure in the Decoding of Violations of Conversational Implicatures
Authors: Tényi T. , Herold R. , Szili I.M. , Trixler M.
Published: April 2003

Objectives: Recent approaches to the ‘theory of mind’ and pragmatics support that, if we did not have any idea about what other people know, we could hardly use language effectively. Successful communication (the pragmatic aspect of language) depends on inferring the beliefs and intentions of the partner in the conversation. Such successful communication is linguistically realized in part by cohesion and in part by abiding by the maxims derived from the cooperative principle. However, the violations of the Gricean implicatures are generally used in everyday language, mainly to point at a hidden, most commonly negative opinion on others. We hypothesize that schizophrenics have difficulties in the decoding of these violations, as the core deficit in this disorder is around social cognition, theory of mind and pragmatic language use. Material and Method: We have examined 26 paranoid schizophrenic patients and 26 normal control subjects by using 4 ‘question and answer’ vignettes, where the Gricean maxim of relevance was violated to express a hidden, negative opinion by one partner during the communicative act. The subjects were asked to judge these opinions and were evaluated by the investigators on a score from 0 to 2 points. In a pilot study, interrater reliability was judged to be satisfactory. The data were analysed statistically by parametric and non-parametric tests. Results: Statistical analyses of our data have shown that schizophrenics made significantly more mistakes during the decoding of the violated maxim as compared with controls (p < 0.0001), reflecting on the difficulties during the correct exploration of the social context, i.e. recognition of the speaker’s hidden opinion. Conclusion: We conclude that patients with schizophrenia fail to decode intentional violations of conversational implicatures. These results point at a dysfunctional pragmatic language use among schizophrenic patients.
Comparison of Psychiatric ICD-10 Diagnoses in Denmark and Germany
Authors: Lange W. , Munk-Jørgensen P. , Bertelsen A. , Schürmann A. , Michels R. , Malchow C.P. , Dilling H.
Published: April 2003

A dataset of psychiatric ICD-10 diagnoses from the Danish case register concerning psychiatric hospitals was compared with a sample of psychiatric diagnoses from 27 psychiatric hospitals in Germany. The comparison shows a higher proportion of F1 diagnoses in the German dataset and a difference in the coding of alcohol dependence and harmful use. Some further differences in the groups F0–F6 are demonstrated and some of them are discussed. The most frequent diagnoses found in both datasets but in different sequence are alcohol dependence syndrome and paranoid schizophrenia and, in third place, adjustment disorder. Various aspects of the problem of rarely used diagnoses are discussed.