bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Features and Revised Diagnostic Criteria in Joubert Syndrome
Authors: Maria Bernard L. , Boltshauser Eugen , Palmer Scott C. , Tran Thang X.
Published: January 2008

The clinical presentation of children with Joubert syndrome can include nonspecific features such as hypotonia, ataxia, and developmental delay. Careful examination of the face shows a characteristic appearance, and a neuro-ophthalmologic examination shows the presence of oculomotor apraxia. In the neonatal period, most children have hyperpnea intermixed with central apnea. Neuroimaging of the head in the axial plane demonstrates the "molar tooth sign"—deep posterior interpeduncular fossa, thick and elongated superior cerebellar peduncles, and hypoplastic or aplastic superior cerebellar vermis. The central nervous system malformation spectrum observed in radiologic and neuropathologic studies accounts for many clinical features of Joubert syndrome. The developmental delay and cognitive impairment cannot be fully explained by the hindbrain malformation and probably result from dysfunction of the cerebral hemispheres. Although related conditions with vermian hypoplasia or aplasia (including Arima; Senior-Loken; and cerebellar vermian hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis syndromes) can mimic Joubert syndrome, detailed imaging data are lacking in such cases. We propose a revision in diagnostic criteria for Joubert syndrome. (J Child Neurol 1999;14:583-591).
Ocular and Oculomotor Signs in Joubert Syndrome
Authors: Tusa Ronald J. , Hove Martin T.
Published: January 2008

A number of oculomotor defects have been described in Joubert syndrome. This study systematically examined the oculomotor systems of 13 individuals previously diagnosed with Joubert syndrome. Twelve had the characteristic "molar tooth sign" seen on magnetic resonance imaging scan. In all individuals, smooth pursuit gain and vestibulo-ocular reflex cancellation were decreased in the horizontal and vertical directions and volitional saccades, when generated, were hypometric. We believe that these defects arise from a disorder in the posterior cerebellar vermis. All individuals also had partial to complete oculomotor apraxia in which initiation of saccades was prolonged or impaired. The oculomotor apraxia in Joubert syndrome differs from congenital idiopathic oculomotor apraxia in that both volitional saccades and quick phases of nystagmus were impaired both in the horizontal and vertical directions, and the defects did not resolve with time. We believe that the oculomotor apraxia arises from a disorder involving the projections from the superior colliculus to the parapontine reticular formation and rostral interstitial nucleus of the medial longitudinal fasciculus. A subset of individuals also had severe visual loss, pendular nystagmus, pigmentary changes in the fundus, and decreased vestibulo-ocular reflexes. We believe that this is a form of Leber's amaurosis occasionally associated with Joubert syndrome. In summary, key oculomotor features of Joubert syndrome are decreased smooth pursuit and vestibulo-ocular reflex cancellation, partial to complete oculomotor apraxia both in the horizontal and vertical directions, and hypometric saccades if oculomotor apraxia is not complete. ( J Child Neurol 1999;14:621-627).
Magnetic Resonance Imaging Features and Classification of Central Nervous System Malformations in Joubert Syndrome
Authors: Quisling Ronald G. , Barkovich A. James , Maria Bernard L.
Published: January 2008

This article examines the magnetic resonance imaging features that typify the Joubert malformation. Specific morphologic features include: (1) dysgenesis of the isthmic portion of the brain stem at the pontomesencephalic junction, (2) abnormally thick superior cerebellar peduncles perpendicular to the brain stem, (3) hypoplasia of the cerebellar vermis with consequent enlargement of the 4th ventricle and rostral shift of the fastigium, and (4) sagittal vermic clefting. At least two of these features were present in every patient and all were present in some. The only cerebral anomaly identified was mild prominence of the ventricles and subarachnoid spaces. The "Joubert-plus anomaly" has been defined as the Joubert malformation plus additional anomalies of either the mesencephalon or the caudal 4th ventricle; this likely represents a similar but more extensive embryologic defect. By placing a relative numeric value on each morphologic feature, a classification scheme has been created that can quantitate the extent of the Joubert malformation in any individual case. ( J Child Neurol 1999;14:628-635).
Autism and Autistic Behavior in Joubert Syndrome
Authors: Ozonoff Sally , Williams Brenda J. , Gale Susan , Miller Judith N.
Published: January 2008

To determine whether individuals with Joubert syndrome exhibit features of autism as defined by the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV), we examined 11 children with Joubert syndrome using the Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule-Generic. Three children met DSM-IV criteria for autistic disorder and one for pervasive developmental disorder not otherwise specified. The other seven all demonstrated at least one DSM-IV symptom of autism, but did not meet criteria for a pervasive developmental disorder. Both total number of DSM-IV symptoms and number of social symptoms distinguished the autism and nonautism subgroups. In contrast, the two subgroups displayed similar levels of communication impairments and repetitive or stereotyped behavior. The key to diagnosing autism in Joubert syndrome is to focus on social behaviors, particularly milestones typically achieved very early in life (eg, attending to human voices, showing objects of interest, enjoyment of social interactions). Implications for the role of the cerebellum in nonmotor behavior and for clinical management of Joubert syndrome also are discussed. ( J Child Neurol 1999;14:636-641).
Joubert Syndrome: Monozygotic Twins With Discordant Phenotypes
Authors: Raynes Hillary R. , Shanske Alan , Goldberg Sharon , Burde Ronald , Rapin Isabelle
Published: January 2008

We describe three sisters with Joubert syndrome, two of whom are monozygotic twins with highly discordant phenotypes. The twins were born at 34 weeks' gestation with discordant birthweights. Their anatomic, neurologic, and developmental status differs greatly: Twin B is able to walk, run, and is verbal, unlike Twin A who is wheelchair-bound, severely retarded, nonverbal, and autistic. Abnormal eye movements and retinal dysplasia are striking features in all three girls, but none has renal cysts seen by ultrasonography. Magnetic resonance images show the "molar tooth sign," the radiologic hallmark of Joubert syndrome, although only one twin, the most severely handicapped, has severe hypoplasia of the cerebellar hemispheres. Phenotypic differences between the twins could be attributable to postzygotic unequal division of the inner cell mass, unequal sharing of the venous return from a monochorionic placenta, mosaicism, or a mutation of a modifying gene. ( J Child Neurol 1999;14:649-654).
Magnetic Resonance Imaging Characteristics of Benign Macrocephaly in Children
Authors: Alper Gülay , Ekinci Gazanfer , Yilmaz Yüksel , Ankan Çiğdem , Telyar Güzide , Erzen Canan
Published: January 2008

Benign macrocephaly of infancy is a common problem in the child neurology practice. The radiologic features of this entity are not well defined. In most of the previous studies, macrocephalic patients were evaluated by computed tomography. To define the radiologic characteristics of this entity, 20 children with macrocephaly with normal neurologic examinations were enrolled in the study. All the patients were evaluated by magnetic resonance imaging studies. Sixty-five percent of patients had enlargement of the subarachnoid space and 35% of patients had megalencephaly. None of the patients had subdural collections. The mean age of patients with enlargement of the subarachnoid space was found to be younger than those with megalencephaly. The cases with parental histories of macrocephaly demonstrated both enlargement of the subarachnoid space and megalencephaly. Our results suggest that the radiologic finding of benign macrocephaly can be both enlargement of the subarachnoid space and megalencephaly. ( J Child Neurol 1999;14:678-682).
Multixnodality Evoked Potential Findings in Infants With Congenital Heart Defects
Authors: Limperopoulos Catherine , Majnemer Annette , Rosenblatt Bernard , Shevell Michael , Rohlicek Charles , Tchervenkov Christo
Published: January 2008

Evoked potentials are sensitive prognostic tools in young infants at risk for developmental disability. The objective of this prospective study was to determine whether infants with congenital heart defects demonstrate evoked potential abnormalities prior to or following open heart surgery, and to examine the association between these abnormalities and developmental status 1 year following surgery. A consecutive series of newborns (less than 1 month old) and infants (1 month to 2 years old) were recruited. Somatosensory and brain stem auditory evoked potentials were carried out before or after cardiac surgery, or both. One year later, neurologic examination and standardized measures of motor performance and functional independence were carried out. Twenty-seven newborns and 31 infants underwent perioperative somatosensory evoked potential recordings. Results indicate that perioperative somatosensory evoked potential abnormalities were common in newborns (41%) but not in infants (13%) with congenital heart defects. Brainstem conduction times were within normal limits in all subjects; however, 32% presented with mild elevations in hearing thresholds. All newborns with abnormal somatosensory evoked potentials had abnormal neurologic examinations both perioperatively and again 1 year after open heart surgery. Moreover, standardized developmental assessments 1 year following surgery indicate that all newborns with somatosensory evoked potential abnormalities had developmental deficits in one or more domains. Somatosensory evoked potential abnormalities in the perioperative period are common in newborns with congenital heart defects, and are strongly predictive of persistent developmental delay later. ( J Child Neurol 1999;14:702-707).
Cognitive and Behavioral Effects of Carbamazepine in Children: Data From Benign Rolandic Epilepsy
Authors: Seidel William T. , Mitchell Wendy G.
Published: January 2008

The effects of antiepileptic drugs on cognition are difficult to delineate, yet of critical importance for children with epilepsy. We investigated the cognitive and behavioral effects of carbamazepine in children with benign rolandic epilepsy. Ten subjects with benign rolandic epilepsy were evaluated with and without carbamazepine treatment. Fourteen unmedicated subjects with migraine headache evaluated twice served as a control group. Subjects were 6 to 12 years of age, fluent in English, and not mentally retarded. We found that children with benign rolandic epilepsy were quicker on a visual-search task and recalled stories better when not treated than when treated with carbamazepine. After correction for multiple comparisons only the memory fmding remained significant. Higher carbamazepine serum level was associated with slower performance on the same visual-search task. This latter finding did not meet multiple comparison criteria. Numerous significant practice effects were found within the control group. Comparisons with reliable change indices identified two subjects with benign rolandic epilepsy with particularly poor scores while receiving carbamazepine. These findings suggest some effects on memory from carbamazepine; however, they do not support meaningful dosage-related effects, within the recommended range. Significant practice effects confirmed the need to control for such effects when evaluating treatments. Finally, identification of two subjects who performed more poorly while on carbamazepine suggests that some children might experience particular difficulties while receiving this medication and highlights the need to investigate individual subject responses to treatment. ( J Child Neurol 1999;14:716-723).
Neurodevelopmental Outcome in Children With Intrauterine Growth Retardation: A 3-Year Follow-Up
Authors: Fattal-Valevski Aviva , Leitner Yael , Kutai Miriam , Tal-Posener Edith , Tomer Abraham , Lieberman Deborah , Jaffa Ariel , Many Ariel , Harel Shaul
Published: January 2008

The study was designed to detect early clinical predictors of developmental outcome in children with intrauterine growth retardation. Eighty-five children with intrauterine growth retardation were followed up prospectively to 3 years of age, using biometric parameters, perinatal risk questionnaires, and neurodevelopmental evaluations. Forty-two children served as controls. A significant difference in neurodevelopmental score at 3 years of age was noted between the intrauterine growth retardation and control groups (P < .001). In the intrauterine growth retardation group, the clinical parameters that most significantly correlated with outcome were cephalization index (head circumference:birthweight ratio), neonatal risk score, and birthweight. The best predictor of 3-year outcome was the cephalization index (P < .01). The children with intrauterine growth retardation with neonatal complications had significantly lower IQ scores (P < .05) and a poorer neurodevelopmental outcome (P < .01) than those without complications. Children with intrauterine growth retardation are at higher risk for developmental disabilities than are controls, especially in the presence of neonatal complications and a high cephalization index. ( J Child Neurol 1999;14:724-727).
Abnormal Visual Evoked Potentials in Children With "Alice in Wonderland" Syndrome Due to Infectious Mononucleosis
Authors: Lahat Eli , Berkovitch Mattityahu , Barr Joseph , Paret Gideon , Barzilai Asher
Published: January 2008

Visual illusions characterized by distortion of form, size, reciprocal position of objects, movement, or color, labeled as "Alice in Wonderland" syndrome, were discussed in children with infectious mononucleosis, as well as in other clinical conditions, such as migraine, epilepsy, use of certain hallucinogenic drugs, etc. The purpose of our study was to investigate for the first time visual evoked potential results in children with "Alice in Wonderland" syndrome associated with infectious mononucleosis. Five children with "Alice in Wonderland" syndrome associated with infectious mononucleosis underwent visual evoked potential studies during and after their clinical symptoms. Visual evoked potential results during the disease demonstrated statistically significant high amplitudes of P 100-N145 in all children compared to the control group. A few weeks later, repeated studies after the resolution of the complaints were normal. Since the same findings can be observed in patients with migraine, we postulate that a common pathophysiologic underlying abnormality, which can cause transient focal decreased cerebral perfusion, could be involved in the disease process of these two conditions. ( J Child Neurol 1999;14:732-735).
A Case of Lafora's Disease Associated With Cardiac Arrhythmia
Authors: Oksel Figen , Tekgül Hasan , Genç Sermin , Özyürek Ruhi , Akalin Tamer , Tütütüncüoğlu Sarenur
Published: January 2008

Progressive myoclonic epilepsies are rare, genetically transmitted diseases characterized by epileptic seizures, myoclonus, and progressive neurologic deterioration. Unverricht-Lundborg disease, Lafora's disease, neuronal ceroid lipofuscinosis, mitochondrial disorders, and sialidosis are included in this group. Lafora's disease is a progressive disorder of the central nervous system with onset in the late first or second decade of life and is inherited in an autosomal-recessive pattern. The first clinical manifestation is generalized tonic-clonic seizures, myoclonus, or both, usually seen between the ages of 11 and 18 years. The other clinical manifestations are progressive dementia and limb ataxia. Diagnosis is based on showing the typical inclusions in the brain, liver, skin, or muscle tissue specimens. The case of a 6-year-old male patient, who was admitted with the clinical findings of third-degree atrioventricular block and dementia and eventually diagnosed with Lafora's disease, is presented. ( J Child Neurol 1999;14:745-746).
Epilepsy With Myoclonic Absences With Early Onset: A Follow-Up Study
Authors: Verrotti Alberto , Greco Rita , Chiarelli Francesco , Domizio Sergio , Sabatino Giuseppe , Morgese Guido
Published: January 2008

We studied six children (four girls and two boys) suffering from cryptogenic myoclonic absence seizures with early onset. The age at onset of the seizures ranged between 6 and 27.8 months (mean age ± SD: 18.5 ± 12.4 months). The neurologic evaluation was normal in all patients at the first hospital admission. After the diagnosis, we followed up all children for at least 5 years. At the end of follow-up, two of these patients (a girl and a boy) showed severe mental retardation, a high number (from one to three per day) of seizures, and persistent pathologic electroencephalograms. The other patients showed normal electroencephalograms: all of them were seizure free and without mental retardation. The two patients with mental retardation have been treated with polytherapy. In all other children we used valproate alone successfully. Our data suggest that myoclonic absence seizures with early onset can have a good long-term prognosis. Valproate is a useful anticonvulsant drug in these patients. Mental retardation is present only in patients with poor seizure control. ( J Child NeuroL 1999;14:746-749).
Factor V1691 G-A, Prothrombin 20210 G-A, and Methylenetetrahydrofolate Reductase 677 C-T Variants in Turkish Children With Cerebral Infarct
Authors: Akar Nejat , Akar Ece , Deda Gulhis , Sipahi Tansu , Orsal Arif
Published: January 2008

Inherited gene defects related to the coagulation system have been reported as risk factors for ischemic stroke. These gene defects include a G-A transition at nucleotide 1691 in exon 10 of the Factor V gene causing activated protein C resistance; a G-A transition in the 3' untranslated region of the prothrombin gene at nucleotide position 20210 (G-A), which is associated with increased levels of prothrombin activity; and a C-T polymorphism at nucleotide 677 in the methylenetetrahydrofolate reductase gene responsible for an alanine to valine substitution, resulting in the synthesis of a thermolabile form of methylenetetrahydrofolate reductase that causes increased levels of homocysteine. The case-control study included 28 patients with cerebral infarction; all were 18 years of age or younger (range, 10 months to 18 years). Seven (25%) of the 28 patients were heterozygous for the FV1691 mutation. Five (17.8%) of the patients carried the PT 20210A mutation. Two (7.1%) of the patients carried both mutations. When compared to controls, the difference was significant for both mutations (P = .007; .04). The frequency of allele T of methylenetetrahydrofolate reductase 677 was 0.3214, which was not significant when compared to controls (0.231; P = .3). A total of 12 (42.8%) patients carried one or both of the mutations FV1691 G-A and PT20210 G-A. From our data, it appears that FV1691 G-A and PT20210 G-A are associated with cerebral infarct risk independently. Risk assessment of double prothrombotic gene alterations did not reveal synergy between these mutations. In conclusion, the presence of FV1691 A and PT20210 A mutations but not the methylenetetrahydrofolate reductase 677 TT mutation correlate with the occurrence of cerebral infarction in children. ( J Child Neurol 1999;14:749-751).
The Effect of Carbamazepine and Sodium Valproate on the Blood and Serum Values of Children From a Third-World Environment
Authors: Hemingway Cheryl , Leary Michael , Riordan Gillian , Schlegal Birgit , Walker Kathleen
Published: January 2008

In third-world countries many children with epilepsy also suffer from malnutrition, anemia, liver disease, and immunosuppression. Doctors might have reservations about the use of anticonvulsants that could aggravate these disorders. The purpose of this study was to establish the prevalence of abnormal blood and serum values in children receiving carbamazepine or sodium valproate as monotherapy who attended a child neurology clinic serving a third-world community in Cape Town, South Africa. Blood samples were taken at routine follow-up visits from 104 children who had been on carbamazepine or sodium valproate monotherapy for at least 6 months. Hematology, serum chemistry, immunoglobulins, and anticonvulsant levels were measured by standard laboratory procedures. Very few subjects had any values outside accepted normal ranges. When clinically indicated and available, carbamazepine and sodium valproate can be prescribed for children from a third-world environment. Frequent blood and serum testing is not necessary in asymptomatic individuals. ( J Child Neurol 1999;14:751-753).
Agenesis of the Corpus Callosum Associated With DiGeorge-Velocardiofacial Syndrome: A Case Report and Review of the Literature
Authors: Kraynack Nathan C. , Hostoffer Robert W. , Robin Nathaniel H.
Published: January 2008

We report a patient with clinical and cytogenetic findings consistent with DiGeorge-velocardiofacial syndrome and agenesis of the corpus callosum. This patient represents the first report of a case of DiGeorge-velocardiofacial syndrome associated with such a central nervous system abnormality. This case, together with previous reports in the literature, suggests that structural brain abnormalities, and in particular abnormalities of the corpus callosum, are part of the complex syndrome associated with the chromosomal microdeletion 22q11.2. We suggest that the diagnosis of DiGeorge-velocardiofacial syndrome be entertained in patients with agenesis of the corpus callosum in the context of other common clinical features of this syndrome. ( J Child Neurol 1999;14:754-756).
Does Status Epilepticus in Children Cause Developmental Deterioration and Exacerbation of Epilepsy?
Authors: Barnard Chantel , Wirrell Elaine
Published: January 2008

The aims of this study were to determine predictors of abnormal outcome, neurodevelopmental deterioration, new-onset epilepsy, refractory epilepsy, and recurrent status epilepticus in children presenting with status epilepticus. For all children presenting to Royal University Hospital, Saskatoon, Saskatchewan, Canada, with status epilepticus between January 1987 and December 1996, demographic data, details of status epilepticus (etiology, duration, treatment, and investigations), developmental milestones, seizures prior to and following status epilepticus, recurrent status epilepticus, and neurologic examination findings at status epilepticus and at follow-up were collected by chart review, patient interview, and neurologic examination. Neurodevelopmental outcome was determined for all subjects except those who died during the initial hospitalization. Predictors of new-onset epilepsy, refractory epilepsy, and recurrent status epilepticus were determined for children followed for 3 months or more after status epilepticus. At follow-up, 79% were abnormal neurologically. Predictors included etiology (nonfebrile or nonidiopathic), perinatal difficulties, preceding developmental delay, abnormal initial neurologic examination; and abnormal neuroimaging. Thirty-four percent showed neurodevelopmental deterioration; predictors included etiology (nonidiopathic or nonfebrile), young age at status epilepticus (12 months or less), and abnormal neuroimaging. Thirty-six percent with no history of seizures preceding status epilepticus developed epilepsy and 25% developed refractory epilepsy. Fifty percent of children had recurrent status epilepticus. In conclusion, very few children presenting in status epilepticus were normal at follow-up. Sequelae were seen predominantly in those with a nonidiopathic, nonfebrile etiology, whereas those with idiopathic or febrile status epilepticus did well. (J Child Neurol 1999;14:787-794).
Cerebral Vasculitis in a Case of Sydenham's Chorea
Authors: Ryan Monique M. , Antony Jayne H.
Published: January 2008

A 10-year-old girl with acute-onset hemichorea had multiple areas of abnormal signal seen on magnetic resonance imaging of the brain, associated with middle and anterior cerebral artery vasculitis seen on cerebral angiography. Her serology and clinical course were supportive of the diagnosis of Sydenham's chorea. Other causes of cerebral vasculitis were excluded. Follow-up studies revealed resolution of changes seen on magnetic resonance imaging and partial resolution of angiographic abnormalities. This is the first report of abnormal cerebral angiography in Sydenham's chorea. ( J Child Neurol 1999; 14:815-818).
Intravenous Valproate Associated With Significant Hypotension in the Treatment of Status Epilepticus
Authors: White James R. , Santos Cesar S.
Published: January 2008

Intravenous valproate has been suggested for the treatment of status epilepticus in part because of its relatively good cardiovascular safety profile. We report a case of severe hypotension associated with intravenous valproate used to treat status epilepticus in an 11-year-old girl. Valproate 960 mg (30 mg/kg) was infused over 1 hour. The patient's blood pressure decreased from a baseline of 130/80 mm Hg to 70/55 mm Hg, 39 minutes into the infusion. Although her seizures stopped, her blood pressure fluctuated between 90/60 mm Hg and 60/30 mm Hg over the next several hours, requiring treatment with intravenous fluids and pressor therapy. Endotracheal intubation eventually was performed. Once her blood pressure stabilized, the patient improved clinically. To our knowledge, this is the first report of significant hypotension associated with intravenous valproate in the treatment of status epilepticus in the pediatric population. ( J Child Neurol 1999;14:822-823).
The Human Heart: Vault of the Soul or Pump?
Authors: Szycher Michael
Published: January 2008

Medical causes that led to the development of artificial hearts are reviewed. Ventricular assist systems are compared with other designs. A discussion of the functioning and surgical implantation of Thermedics Corporation's ventricular assist pump provides a context for an analysis of technical challenges still to be solved.
Mechanical Support for the Failing Heart
Authors: Altieri F.D. , Watson J.T. , Taylor K.D.
Published: January 2008

The National Heart, Lung, and Blood Institute (NHLBI) has sponsored considerable research directed toward basic studies on the etiology of heart disease and atherosclerosis. While progress has been very encouraging there are still significant numbers of patients with end-stage heart disease. NHLBI initiated goal-oriented research activities on the artificial heart based upon the recommendation of the National Heart Advisory Council in 1964. The major goal of the Artificial Heart Program was to develop devices which could be effectively used to rehabilitate patients with end-stage heart disease. This paper will describe the evolution and specific program goals of the Artificial Heart Program and provide a description of the left ventricular assist stystem (LVAS) and total artificial heart (TAH) research efforts. Specific attention will be directed toward defining device requirements, descriptions of the blood pump and energy converter, control system operation and energy transmission methods. A summary of experimental results and current development status will also be provided.
Hercon Technology for Transdermal Delivery of Drugs
Authors: Shah Kishore R. , Ng Shirley , Zeoli Laura , Haight Valerie , Matz Sheila , Kydonieus Agis F.
Published: January 2008

The Hercon controlled drug delivery technology is based on a multi-layered laminated polymeric structure, in which a layer of vinyl chloride copolymer or terpolymer containing the drug is sandwiched between two or more layers of polymeric films. The drug is released from the device at a controlled rate by a process of diffusion through the reservoir and one of the outer layers, which can function as a rate controlling membrane. This basic technology has been successfully utilized for the development and commercialization of Nitroglycerin Transdermal System (NTS, Bolar Pharmaceutical Co., Inc). In vitro and in vivo investigations of transdermal delivery of different other drugs from the Hercon polymeric devices have indicated the feasibility of using this system to meet a variety of therapeutic needs.
Autooxidative Degradation of Implanted Polyether Polyurethane Devices
Authors: Stokes Kenneth , Coury Arthur , Urbanski Peter
Published: January 2008

While certain polyether polyurethanes have been shown to be biostable, undesirable interactions between polymer, the body environment and device can occur. For example, the corrosion products of metallic parts can cause relatively rapid autooxidation of polyether soft segments. This phenomenon was first demonstrated in our laboratories by immersing polyurethane test specimens in metal ion solutions of different oxidation potentials. Subsequently, the mechanism was reasonably duplicated by immersing Pellethane 2363-80A insulated cardiac pacing leads in 3%, 37°C hydrogen peroxide. In vivo studies after 1 year show that corrosion products from pure Co and Fe produce the most rapid degradation of the polyurethane.
Poly(ether) Urethane Reactivity with Metal-Ion in Calcification and Environmental Stress Cracking
Authors: Thoma Randall J.
Published: January 2008

Since their introduction to the biomedical community in 1967, polyurethanes have been used in a number of biomedical applications. In chronic applications evidence is now available which suggests that polyurethanes may be subject to various cracking phenomena. Environmental stress cracking and calcification are two phenomena resulting in poly(ether)urethane cracking, which have been shown to be enhanced by ion complexation.

Much evidence now exists which defines the ability of poly(ether)urethanes to selectively extract ions, especially calcium ion from solution. Metal ion binding appears to enhance environmental stress cracking and appears to be a first step in the process of calcification.
Chemical Modification of Polyurethanes by Radiation-Induced Grafting
Authors: Jansen Bernd
Published: January 2008

Basic methods of radiation-induced modification of polyurethanes for biomedical applications and of their characterization are briefly described. The most important works found in literature on radiation grafting of polyurethanes are discussed.

The radiation grafting of polyetherurethane films and tubings by the pre-swelling method using various monomers and their physico-chemical characterization are discussed in detail with respect to the antithrombogenic properties of the materials.

Novel applications for radiation-modified polyurethanes as drug delivery systems or antiinfectious materials are briefly mentioned.
Clinical Behavior of Composite Resins
Authors: Leinfelder Karl F. , Osborne John W.
Published: January 2008

Since the original development by Bowen in the 60's, composite resins have evolved into a widely used and successful restorative material. Although they exhibit certain inadequacies as a dental restorative material, improvements constantly are being made. Due to the aesthetic nature of the material, coupled with its potential for mechanical and chemical bonding to tooth structure, composite resins will become more broadly used in the future.
Fluoride-Releasing Acrylics
Authors: Ralph Rawls H.
Published: January 2008

There are numerous examples in dentistry where demineralization, or even frank caries, develops near or in association with restorative or prosthetic materials. Leaking cavity margins and demineralization under bite splints are two examples. A slow-release source of fluoride could help to prevent these problems and provide added protection throughout the mouth. For this purpose a family of fluoride-releasing resins has been developed for use in various adhesive applications, and also for preparing temporary crowns and removable acrylic devices. These materials contain fluoride ions held to covalently bound positive charge sites within the polymer network. Release is by a diffusion/exchange mechanism in which anions from oral fluids diffuse to the charge sites and exchange with fluoride. Fluoride then diffuses to the surface and is released into solution. This method of release allows for the retention of adequate physical properties and is capable of a linear release rate for terms ranging from days to years.
Application of Expanded Polytetrafluoroethylene (ePTFE) Tubing to the Study of Human Wound Healing
Authors: Goodson William H.
Published: January 2008

Wounds are a part of daily life. They range from minor nicks and cuts to the incisions of major surgery. In the sequence of evolution the process of healing arose long before modern science. The events which we are beginning to unravel have occurred routinely for a very long time despite our lack of understanding. We have learned how to nurture healing, but how to modify healing in a positive sense is only an approaching reality. Standardized tests of human healing are a necessary part of future research in wound healing. In the Wound Healing Laboratory we have used tubes of expanded polytetrafluoroethylene (ePTFE) as a tissue-sampling device in small, experimental, needle-stick wounds. Ingrowth into ePTFE is influenced by surface and structural characteristics. These are held constant, and "normal" values can be established and used as a base with which to study effects of various clinical states on healing in humans.
Tissue Response to Biodegradable Injectable Microcapsules
Authors: Visscher G.E. , Robison R.L. , Argentieri G.J.
Published: January 2008

Biodegradable microcapsules have been shown to be capable of delivering a sustained release of various medicinal agents. We have observed an initial minimal, sharply localized, acute inflammatory response to intramuscularly injected microcapsules produced from various polymers. Evaluation of later time points has shown a diminishing macrophage, foreign body giant cell, and connective tissue response along with actual microcapsule degradation. No fibrous capsule formation was seen. Complete resolution of the tissue reaction can be expected, with the time frame depending upon the polymer utilized. Published experimental results report similar minor tissue responses to a variety of injected biodegradable microcapsules.
Strategies for Biological Testing of Biomaterials
Authors: Northup Sharon J.
Published: January 2008

Current perspectives on empirical, modeling, and mechanistic methods of medical device safety testing are reviewed. Empirical approaches, such as the U.S. Pharmacopeial biological tests for plastics, evaluate the total system to discover aberrations and abnormalities. Models consist of a single aspect of an integrated approach, whereas mechanistic methods are based on a thorough knowledge of the materials and the organism's biological response. Empirical studies develop data on general hazard potential, such as overt toxicity. Model approaches target the specific application and specific hazard potential. Mechanistic studies identify the cause of toxicity and can produce advances in the biocompatibility of medical devices.
A Review of Structural and Material Properties of Vascular Grafts
Authors: Pourdeyhimi B. , Text C.
Published: January 2008

A brief review of the textile structures employed in the construction of vascular grafts is followed by a survey of the causes of failure cited in the literature. An attempt is made to determine the structural factors contributing to the failure of vascular grafts, and attention is given to material properties and methods for determining these attributes. Need for further research is emphasized.
Introduction of Surface Functional Groups onto Biomaterials by Glow Discharges
Authors: Sharma Chandra P. , Jayasree G. , Najeeb P.P.
Published: January 2008

An attempt was made to graft the monomer HEMA to the polymer surface by "Glow discharge" technique. Experiments were carried out for different surfaces varying the exposure times of samples to HEMA and also as a function of glow discharge time. It was found that as the percentage of grafting increases the hydrophilicity also increases. Contact angle measurements were performed on these substrates, which confirmed the hydrophilic nature of the grafted samples compared to the controls.

The role of protein adsorption and their effects to modulate the blood polymer interaction is briefly discussed. When a foreign material comes in contact with blood, the initial event is the adsorption of plasma proteins in parallel with the adhesion of platelets to the material. Albuminated surfaces discourage platelet adhesion while fibrinogen enhances the platelet attachment and thrombosis. Hence a decreased ratio of fibrinogen to albumin on a substrate can be correlated as an indication to its improved blood compatibility. Fibrinogen to albumin ratios of the grafted samples showed a reduction, indicating that albumin adsorption is high; which may make the modified surfaces non-thrombogenic.
Hemocompatibility of Hydrogel with Polyethyleneoxide Chains
Authors: Nakao Akimasa , Nagaoka Shoji , Mori Yuichi
Published: January 2008

We have synthesized a hydrogel with long polyethyleneoxide (PEO) chains and evaluated its hemocompatibility. The hydrogel significantly suppressed the adsorption of plasma proteins and adhesion of platelets. In addition, the marked retardation of thrombus formation on its surface was recognized. These findings seems to be caused by the volume restriction effects derived from the highly flexible and hydrophilic PEO chains.
Antithrombogenic Heparin-Bound Polyurethanes
Authors: Ito Y.
Published: January 2008

Many kinds of heparin-bound polyurethanes have been developed. Polyurethanes are a family of elastomers displaying better blood-compatibility than other polymeric materials. It is useful to modify this material by heparinization. Several approaches to heparinization have been devised: 1) a general method of heparinization, applicable to all polymeric materials, 2) a heparinization method specific to polyurethanes, and 3) the design of heparinizable polyurethane derivatives.

These three approaches are first explained in detail. Then, the antithrombogenic mechanism of the heparinized polymers is discussed. Finally, the interactions of the heparinized polymers with blood coagulation factors, plasma proteins, and platelets are discussed.
Controlled Release of Diphosphonates from Synthetic Polymers to Inhibit Calcification
Authors: Golomb Gershon
Published: January 2008

Calcification is the most frequent cause of the failure of bioprosthetic heart valves fabricated from glutaraldehyde pretreated porcine aortic valves or bovine pericardium. Formulation and evaluation of controlled-release drug delivery system to inhibit bioprosthetic heart valve calcification is reviewed.
Blood Compatible Polyurethane Elastomers
Authors: Szycher Michael , Griffin Joseph C. , Williams Joel L. , McMenamy James P. , Stagg D.
Published: January 2008

Medical applications of blood compatible polyurethane elastomers contribute significantly to the quality and effectiveness of the nation's health system. These projects range from artificial hearts to diagnostic/therapeutic cardiac catheters which are saving the lives of many critically ill patients.
Biomaterials Entrepreneurship
Authors: Ellis Jeffrey R.
Published: January 2008

Entrepreneurial companies in biomaterials serve a valuable function in lowering the risk of developing new products and devices. In many cases liability considerations and a pragmatic conservatism make it difficult for established health-care products suppliers to develop new products directly. Biomaterials entrepreneurs encounter more difficulties in achieving commercial success than do entrepreneurs in other fields. For any reasonable profit to be made, the entrepeneur must be able to convert the biomaterial into a useful device. Safety and toxicity test data collection take a minimum of three years to collect, and it is often five or more years before a positive cash flow can be obtained. Start-up funding can be obtained from government agencies, charitable foundations, and private investment capital. A major health-care company can often be attracted once initial successes have been achieved.

Biomaterials usage and device design is specific for each function or need. Specific devices that are currently needed are small (c. 4 mm) diameter artificial blood vessels, synthetic skin, and internal prosthetic devices which have better tissue compatibility, abrasion, corrosion, and wear resistance especially for flexing devices such as artificial joints, ligaments and tendons.
Porous Collagen Sponge Wound Dressings: in vivo and in vitro Studies
Authors: Doillon Charles J.
Published: January 2008

Collagen-based materials can be formed into a three-dimensional sponge for use as a wound dressing and as a support for cell cultured skin components. Factors such as biocompatibility, morphological structure and addition of non-collagenous molecules to collagen are analyzed and discussed. Large pores or channels, interchannel communications and combinations of macromolecules of the connective tissue enhance wound tissue infiltration in vivo as well as cell growth in vitro into collagen sponges. The presence of such factors can be useful in patients with excised burn wounds and pressure skin ulcers.
Advances in Prosthetic Heart Valves: Fluid Mechanics of Aortic Valve Designs
Authors: Yoganathan Ajit P. , Woo Yi-Ren , Sung Hsing-Wen , Jones Michael
Published: January 2008

The in vitro hemodynamic characteristics of a variety of mechanical and tissue heart valve designs used during the past two decades were investigated in the aortic position under pulsatile flow conditions. The following valve designs were studied: Starr-Edwards ball and cage (model 1260), Björk-Shiley tilting disc (convexo-concave model), Medtronic-Hall tilting disc, St. Jude Medical bileaflet, Carpentier-Edwards porcine and pericardial (models 2625, 2650 and 2900), Hancock porcine (models 250 and 410) and Ionescu-Shiley standard pericardial. The Starr-Edward ball and cage, Björk-Shiley tilting disc, Carpentier-Edwards porcine (model 2625) and Ionescu-Shiley standard pericardial valves were designed prior to 1975, while the Medtronic-Hall tilting disc, St. Jude Medical bileaflet, Hancock porcine (model 250), Hancock II porcine (model 410), Carpentier-Edwards porcine (model 2650) and Carpentier-Edwards pericardial (model 2900) valves were designed after 1975. The pressure drop results indicated that the valves designed prior to 1975 had performance indices of 0.30 to 0.45, whereas the valves designed after 1975 had performance indices of 0.40 to 0.70. The regurgitant volumes were higher for the mechanical designs (5.0 to 11.0 cm3/beat) compared to the tissue bioprostheses (1.0 to 5.0 cm3/ beat). Two-dimensional laser Doppler anemometry studies indicated that the valves designed after 1975 tended to create more centralized flow fields, with reduced levels of turbulent shear stresses. However, none of the current valve designs is ideal: they all create areas of stasis and/or regions of low velocity reverse flow; and regions of elevated turbulent shear stresses that are capable of causing sub-lethal and/or lethal damage to the formed elements of blood.
Artificial Cells as Bioreactive Biomaterials
Authors: Chang Thomas Ming Swi
Published: January 2008

Artificial cells can have the same dimensions as biological cells. They can enclose and retain a large variety of bioreactants. Artificial cell membranes can have the required permeability characteristics to allow the rapid equilibration of external molecules to be acted on by the enclosed bioreactants. Polymer, protein, protein-lipid, polymer-lipid, lipid or other materials can form artificial cell membranes. It is possible to vary the membrane thickness and permeability characteristics over a wide range. Many different forms of bioreactive artificial cells are available. This article contains only a few examples. This includes its applications in (1) red blood cell substitutes; (2) immobilisation of enzymes, multienzymes with cofactor recycling, cell cultures and other biotechnological applications; (3) hemoperfusion in kidney failure, poisoning, removal of aluminium and iron; (4) use in liver failure; (5) other applications in microencapsulation.
Factors and Interactions Affecting the Performance of Polyurethane Elastomers in Medical Devices
Authors: Coury Arthur J. , Slaikeu Paul C. , Cahalan Patrick T. , Stokes Kenneth B. , Hobot Christopher M.
Published: January 2008

Polyurethanes offer the greatest versatility in compositions and properties of any family of polymers. For implantable medical devices, a few specific elastomeric polyurethane compositions have demonstrated a combination of toughness, durability, biocompatibility and biostability not achieved by any other available material.

Because of the complex behavior of implantable polyurethanes in the body environment, designers and fabricators of polyurethane-containing devices must pay particular attention to the choice of composition and design of components. Subsequent treatment during qualification, fabrication, sterilization, storage, implantation, in vivo operation and explantation also determine the performance and provide the means for assessing the efficacy of the polyurethane in the implanted device.
Biomedical Applications of Polyurethanes: Implications of Failure Mechanisms
Authors: Phillips R.E. , Smith M.C. , Thoma R.J.
Published: January 2008

Three mechanisms have been described which explain various observed interactions between polyurethane chemistry and body chemistry. These include calcification, environmental stress cracking, and chain scission. Each may result in implant device failure, and each appears to involve metal ion complexation as a key parameter. Continued expansion of polyurethane into implantable product applications will require further clarification of the effect of each of these interactions on long-term product performance. It is believed that design considerations and polymer modifications will help control the effects of each of the interactions and will result in new and improved polyurethane implant products.
Polyether Polyurethanes: Biostable or Not?
Authors: Stokes Kenneth B.
Published: January 2008

Certain polyether polyurethanes have been shown to be biostable in long-term implant studies. Others retain good bulk properties, but have been shown to develop cracks on their tissue contacting surfaces. Two cracking mechanisms have been identified, in vivo stress cracking and metal ion oxidation. Stress cracking is the result of an interaction between the in vivo mammalian environment and residual stress (strain) in the implanted polymer. Mild autooxidation can be initiated by stress cracking. More extensive autooxidation can be initiated and propagated by corrosion of metallic device components, especially the corrosion products of cobalt. Both mechanisms are controllable, thus, do not necessarily preclude the use of polyether polyurethanes in implantable devices.
The Evolution of the Intra-Aortic Balloon: The Datascope Contribution
Authors: Wolvek Sidney
Published: January 2008

The first clinical use of the intra-aortic balloon was reported in 1968. In the ensuing twenty years it has become the most commonly used cardiac assist device. The evolution of the balloon catheter, its driving console and the indications for its use during the past two decades are reviewed.