Ivory osteoma of the craniofacial skeleton

The authors describe the clinical presentation, investigation, and surgical management of two cases of benign ivory osteoma of the craniofacial skeleton. In the first case, a bony mass located over the frontal region had become a cosmetic burden to the patient, and she requested removal with minimal morbidity. Accordingly, an endoscopic procedure, with minimal access incisions located behind the hairline, was devised. In the second case, the patient, a Jehovah's Witness, presented with a long history of slowly enlarging bony masses over the maxilla and in the pterygopalatine space. She finally requested surgical intervention when the symptoms of pain related to fifth nerve compression at the foramen ovale became intolerable. Key aspects of the preoperative and perioperative management strategies used to avoid blood transfusion are detailed, as is the surgical approach, which included a bicoronal scalp flap with temporary removal of the zygomatic arch and the coronoid process. Finally, the etiology, histology, and natural history of ivory osteomas are discussed.     

Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma.

PURPOSE: To describe the clinical studies, chemistry manufacturing and controls, and clinical pharmacology and toxicology that led to Food and Drug Administration approval of nelarabine (Arranon) for the treatment of T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma. EXPERIMENTAL DESIGN: Two phase 2 trials, one conducted in pediatric patients and the other in adult patients, were reviewed. The i.v. dose and schedule of nelarabine in the pediatric and adult studies was 650 mg/m2/d daily for 5 days and 1,500 mg/m2 on days 1, 3, and 5, respectively. Treatments were repeated every 21 days. Study end points were the rates of complete response (CR) and CR with incomplete hematologic or bone marrow recovery (CR*). RESULTS: The pediatric efficacy population consisted of 39 patients who had relapsed or had been refractory to two or more induction regimens. CR to nelarabine treatment was observed in 5 (13%) patients and CR+CR* was observed in 9 (23%) patients. The adult efficacy population consisted of 28 patients. CR to nelarabine treatment was observed in 5 (18%) patients and CR+CR* was observed in 6 (21%) patients. Neurologic toxicity was dose limiting for both pediatric and adult patients. Other severe toxicities included laboratory abnormalities in pediatric patients and gastrointestinal and pulmonary toxicities in adults. CONCLUSIONS: On October 28, 2005, the Food and Drug Administration granted accelerated approval for nelarabine for treatment of patients with relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma after at least two prior regimens. This use is based on the induction of CRs. The applicant will conduct postmarketing clinical trials to show clinical benefit (e.g., survival prolongation).     

Torticollis associated with positional plagiocephaly: a growing epidemic

The primary study aim was to identify characteristics of torticollis associated with plagiocephaly without synostosis (PWS) and to differentiate this from other forms of torticollis. The three commonest causes of infantile torticollis are idiopathic muscular causes such as sternocleidomastoid fibrosis, structural anomalies in the cervical vertebrae, and neurologic or ocular causes, such as certain types of strabismus. Recently, several units have reported increasing numbers of babies presenting with head tilt and reduced range of cervical motion, a form of torticollis apparently associated with PWS and unrelated to the etiologies enumerated above. A secondary aim was to identify local trends in referral patterns over the preceding 3 years. This was a retrospective review of 159 children attending a secondary referral center for management of positional plagiocephaly or torticollis. The data was collected in a university-affiliated child development clinic, and the records of one of three similar, community-based outpatient clinics, staffed by physical therapists and working in conjunction with our tertiary craniofacial surgery center were analyzed by medical staff. There was a persistent escalation in referrals for both PWS and associated torticollis (ie, not attributable to 1 of the 3 causes mentioned) over the study period. Anatomic and clinical features of PWS-associated torticollis were characterised and contrasted with the classic forms of torticollis. Current treatment strategies are outlined and discussed. Torticollis can predispose to PWS, but in a large proportion of our cases of PWS, torticollis appears to develop secondary to plagiocephaly, and the number of presentations is escalating.     

LH3, a "homologue" of the mastadenoviral E1B 55-kDa protein is a structural protein of atadenoviruses

Ovine adenovirus serotype 7 (OAdV), the prototype atadenovirus, has gene homologues for most mastadenovirus structural proteins but lacks proteins V and IX. Instead, OAdV has structural proteins of 32 and 42 kDa although the gene encoding the latter had not previously been identified. The presently reported studies of OAdV virions have now identified a minor structural polypeptide of approximately 40 kDa as the product of the L1 52/55-kDa gene and, more surprisingly, shown that the 42-kDa protein is encoded by LH3. This gene product was previously thought to be a homologue of mastadenovirus E1B 55 kDa, which is a multi-functional, non-structural protein that cooperates with E1A in cell transformation. The lack of transforming activity previously demonstrated for OAdV combined with a structural role for the LH3 product indicates that the protein has a different function in atadenoviruses. We discuss the abundance and likely core location of LH3 in the virion and the possible derivation of the E1B 55-kDa gene from the LH3 gene.     

Dynamic reorganization of the astrocyte actin cytoskeleton elicited by cAMP and PACAP: a role for phosphatidylInositol 3-kinase inhibition

Cyclic AMP (cAMP)-raising agents induce astrocytes grown in vitro to adopt a stellate morphology resembling their in vivo appearance, through the depolymerization of actomyosin stress fibres. The signalling pathways responsible for cAMP-induced astrocyte stellation have thus far remained largely elusive. We showed in this study that the neurotrophic peptide PACAP (pituitary adenylate cyclase-activating polypeptide) mimicked the effect of forskolin, a direct activator of adenylate cyclase, on the actin cytoskeleton of primary rat astrocytes. The depolymerization of stress fibres induced by PACAP or forskolin was prevented by the expression of a constitutively active mutant of RhoA, but not by a protein kinase A (PKA) blocker, indicating that cAMP-raising agents act upstream of RhoA, in a PKA-independent manner. In addition, PACAP and forskolin inhibited basal Akt phosphorylation, and basal and epidermal growth factor (EGF)-stimulated phosphatidylinositol 3-kinase (PI 3-K) activities. Incubation with a PI 3-K blocker resulted in the depolymerization of stress fibres. This effect was blocked by the expression of a constitutively active mutant of RhoA, indicating that PI 3-K inhibition acted upstream of RhoA. Together, these data demonstrate for the first time that depolymerization of stress fibres, and the resulting astrocyte stellation, induced by stimulation of cAMP production involves the inhibition of the PI 3-K-RhoA pathway.     

Assessing level of consciousness and cognitive changes from vegetative state to full recovery

Although investigations addressing cognitive recovery from the vegetative state have been reported, to date there have been no detailed studies of these patients combining both neuropsychology and functional imaging to monitor and record the recovery of consciousness. This paper describes the recovery of a specific vegetative state (VS) case. The patient (OG) remained in the vegetative state for approximately two months, increasing her level of awareness to a minimally conscious state, where she continued for approximately 70 days. In the course of the ensuing 18 months, she was able to reach an acceptable level of cognitive functioning, with partial levels of independence. Throughout this two year period, she received continuous cognitive evaluation, for which several different tools were applied including coma and low functioning scales, full cognitive batteries, and structural and functional magnetic resonance imaging (MRI). We present here preliminary data on fMRI using a word presentation paradigm before and after recovery; we also discuss the difficulty of how to determine level of consciousness using the tools currently available, and the subsequent improvement in different cognitive domains. We confirm that accurate diagnosis and proper cognitive assessment are critical for the rehabilitation of patients with disorders of consciousness.     

Autism spectrum traits in children with mood and anxiety disorders

The autism spectrum disorders (ASDs) can present with symptoms commonly found in mood and anxiety disorders. The Social Communication Questionnaire (SCQ), Children's Communication Checklist (CCC-2), and the Social Reciprocity Scale (SRS) were used to screen children in a mood disorders research clinic setting for symptoms of ASD. Ninety-three patients (mean age, 12.7 +/- 2.8 years; percent male, 63%) completed at least one scale, and 50 children completed all three. The prevalence of those screening positive for a possible ASD on one instrument was 62% and on all three measures was 8%. Fifty-seven percent (n = 21/37; odds ratio, 4.59 [95% confidence interval (CI) = 1.40-15.11]) of those scoring in the "ASD-likely" range on the SRS scored in that range on the CCC-2. Only 16% (n = 6/37; odds ratio, not significant (NS)) of those scoring in the ASD-likely range on the SRS, and 14% (n = 5/37; odds ratio, NS) of those scoring in the ASD-likely range on the CCC-2, scored similarly on the SCQ. These results demonstrate a need to develop valid and reliable instruments to screen for ASDs in children presenting outside of ASD clinics.