[Hypophosphatemia as a prognostic measure of evaluation].
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Diabetic Ketoacidosis↗
Biomedical subjects
B Gordon
Publications and source records attributed to B Gordon.
Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype.
We report the results of genetic analysis on a series of 51 patients attending this Haemophilia Comprehensive Care Centre. The most common cause of severe haemophilia A--the factor VIII intron 22 inversion was detected in eight families and the factor VIII intron 1 inversion in three families. Mutation analysis was carried out on the remaining patients by nucleotide sequencing of genomic DNA after screening with conformation-sensitive gel electrophoresis (CSGE) or denaturing high-performance liquid chromatography (dHPLC). A total of 27 different FVIII non-inversion mutations were detected. Severe haemophilia was associated with 12 null mutations (six nonsense, six frameshift) and four missense mutations. A further 11 different missense mutations were associated with moderate or mild disease. To our knowledge, six null mutations [1950del 4(tttg), 3270-75insA, 4416del 10, 6735-38delA, W1029X, Y1792X] and four missense mutations (E1682K, M1947V, P2048L, P2143L) have not been previously published. Each novel missense mutation occurred at a highly conserved residue, no other candidate mutation was detected on screening the entire coding region of the FVIII gene and they were not detected in a screen of individuals without haemophilia A. The genotype-phenotype correlations of the FVIII mutations detected will be discussed.
Base Sequence↗
Electrocorticographic gamma activity during word production in spoken and sign language.
OBJECTIVE: To investigate the functional-neuroanatomic substrates of word production using signed versus spoken language. METHODS: The authors studied single-word processing with varying input and output modalities in a 38-year-old woman with normal hearing and speech who had become proficient in sign language 8 years before developing intractable epilepsy. Subdural electrocorticography (ECoG) was performed during picture naming and word reading (visual inputs) and word repetition (auditory inputs); these tasks were repeated with speech and with sign language responses. Cortical activation was indexed by event-related power augmentation in the 80- to 100-Hz gamma band, and was compared with general principles of functional anatomy and with subject-specific maps of the same or similar tasks using electrical cortical stimulation (ECS). RESULTS: Speech outputs activated tongue regions of the sensorimotor cortex, and sign outputs activated hand regions. In addition, signed word production activated parietal regions that were not activated by spoken word production. Posterior superior temporal gyrus was activated earliest and to the greatest extent during auditory word repetition, and the basal temporal-occipital cortex was activated similarly during naming and reading, reflecting the different modalities of input processing. With few exceptions, topographic patterns of ECoG gamma were consistent with ECS maps of the same or similar language tasks. CONCLUSIONS: Spoken and signed word production activated many of the same cortical regions, particularly those processing auditory and visual inputs; however, they activated different regions of sensorimotor cortex, and signing activated parietal cortex more than did speech. This study illustrates the utility of electrocorticographic gamma for studying the neuroanatomy and processing dynamics of human language.
Brain Mapping↗
Alterations in osteoclast morphology following long-term 17beta-estradiol administration in the mouse.
BACKGROUND: Although the role of the osteoclast in bone resorption is becoming better understood, much remains to be learned about osteoclastogenesis and the exact mechanism of action of anti-resorbing agents such as 17beta-estradiol. This study investigated bone and morphologic osteoclast alterations following long-term estrogen administration to the B6D2F1 mouse. B6D2F1 mice aged 4-5 weeks were exposed to high levels of estrogen via implanted silastic tubing for at least 12 weeks; controls received empty tubing. Femurs of control and treated mice were assessed with radiology, quantitative histomorphometry and transmission electron microscopy. RESULTS: After 8 weeks of treatment, there was radiologic evidence of severe osteosclerosis and 86% of femoral marrow space was replaced with bone. After 12 weeks histologic studies of treated animals revealed that osteoclasts were positive for tartrate-resistant acid phosphatase but showed markedly abnormal ultrastructure which prevented successful bone resorption. CONCLUSIONS: Findings extend our understanding of osteoclast structure and function in the mouse exposed in vivo to high doses of estrogen. Ultrastructural examination showed that osteoclasts from estrogen-treated mice were unable to seal against the bone surface and were unable to form ruffled borders.
Acid Phosphatase↗
Traumatic atlantoaxial distraction injury: a case report.
STUDY DESIGN: Case report. OBJECTIVES: Description of a rarely reported variant of traumatic C1-C2 dislocation and discussion of a favorable outcome in a nonsurgical treatment approach. SUMMARY OF BACKGROUND DATA: Atlantoaxial dislocation most commonly involves an anterior movement of C1 in relation to C2. Often, the integrity of the transverse ligament or odontoid process is compromised, and the atlantodental interval changed. The described patient sustained a purely craniocaudal atlantoaxial distractive lesion secondary to injury sustained in a high-speed motor vehicle accident. RESULTS: The initial treatment plan involved surgical stabilization subsequent to healing of a C1 ring fracture. After 12 weeks of external stabilization, ligamentous damage appeared well resolved. That there was no gross instability delayed using a surgical option. At periodic checkup, the patient was without symptoms. CONCLUSION: In this case, conservative management of a ligamentous C1-C2 injury was effective. At 5 years after trauma the patient was without sequelae. This outcome is in contrast to previous management of injuries of this type, all of which involved surgical intervention.
Accidents, Traffic↗
Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease.
BACKGROUND: Donepezil hydrochloride is a selective acetylcholinesterase inhibitor approved for the symptomatic treatment of mild to moderately severe Alzheimer disease (AD). Controlled clinical trials of up to 24 weeks have demonstrated that donepezil treatment (5 and 10 mg/d) significantly improves cognition and global function. OBJECTIVE: To investigate the long-term benefits of donepezil treatment in patients with AD. DESIGN: Multicenter, open-label, 144-week extension of 2 US phase 3, double-blind, placebo-controlled clinical trials: a 15-week study (12 weeks of treatment followed by a 3-week placebo washout) and a 30-week study (24 weeks of treatment followed by a 6-week placebo washout). INTERVENTIONS: All patients (N = 763) initially received donepezil, 5 mg/d, for 6 weeks, after which an increase to 10 mg/d was encouraged. MEASURES: Primary efficacy measures were the Alzheimer's Disease Assessment Scale-cognitive subscale and the Clinical Dementia Rating-Sum of the Boxes. RESULTS: After the shorter 3-week placebo washout, donepezil-associated benefits remained above original baseline values for an additional 24 weeks of open-label treatment. Benefits on Alzheimer's Disease Assessment Scale-cognitive subscale scores for patients who received 10 mg/d in the double-blind study were evident compared with the other groups for 108 weeks of open-label treatment. In contrast, donepezil-associated benefits were lost after the 6-week placebo washout, and scores decreased below original baseline values for all patient groups. Although scores improved relative to the new open-label study baseline scores after drug use was restarted, patients remained below original baseline values. The most common adverse events were associated with the nervous and digestive systems and were generally mild and transient; 17% of patient discontinuations were associated with adverse events. CONCLUSIONS: Donepezil is an effective and safe drug for the long-term symptomatic treatment of mild to moderately severe AD for up to 144 weeks (2.8 years), and sustained treatment may confer some advantages.
Aged↗
Induced electrocorticographic gamma activity during auditory perception. Brazier Award-winning article, 2001.
OBJECTIVE: To define the spatial, temporal, and functional characteristics of induced gamma (>30 Hz) activity during functional activation of the left superior temporal gyrus. METHODS: Electrocorticographic (ECoG) recordings were made in 4 clinical subjects during auditory tone and phoneme discrimination tasks, and event-related changes in the ECoG band power were calculated. The topography and temporal sequence of event-related power changes in different gamma bands were contrasted with those of auditory evoked potentials (AEPs), and with those of event-related power changes in the alpha band (8-12 Hz). RESULTS: Auditory stimuli induced a broadband power augmentation that included 40 Hz, as well as higher (80-100 Hz) gamma frequencies. The topography of gamma augmentation was similar, but not identical, to that of the AEP, and was more focused than that of alpha power suppression. Its temporal onset coincided with the N100, but outlasted it. Phonemes produced greater gamma augmentation than tones, while a similar difference was not observed in the N100. CONCLUSIONS: Auditory perception induces ECoG gamma activity not only at 40 Hz, but also in higher gamma frequencies. This activity appears to be an index of cortical activation that reflects task-specific processing in the human auditory cortex more closely than the AEP or alpha power suppression.
Adolescent↗
The Ipswich childbirth study: one year follow up of alternative methods used in perineal repair.
OBJECTIVE: To assess the long term implications of four alternative approaches to postpartum perineal repair. DESIGN: A stratified randomised controlled trial using a 2x2 factorial design. SETTING: Original recruitment at the Maternity Unit at Ipswich Hospital NHS Trust, a district general hospital, between 1992 and 1994. SAMPLE: Seven hundred and ninety three women who had participated in the Ipswich Childbirth Study--a trial among women who had required repair of episiotomy or first or second degree tears--at least one year previously. METHODS: Self-completed postal follow up at least one year after recruitment to trial comparing 1. two-stage repair leaving the skin unsutured with standard three-stage repair, and 2. polyglactin 910 with chromic catgut as suture material for the repair. MAIN OUTCOME MEASURES: Failure to resume pain-free intercourse; persistent perineal pain; perineum feeling different; resuturing; time to resume pain-free intercourse; and dyspareunia. RESULTS: Fewer women allocated two-stage repair reported that the perineum felt different (30% versus 40%; RR 0.75; 95% CI 0.61 to 0.91; 2P < 0.01); otherwise there were no clear differences between the two methods. Women allocated polyglactin 910 were less likely to have dyspareunia (8% versus 13%; RR 0.59, 95% CI 0.39 to 0.91; 2P = 0.02) and less likely to fail to resume pain-free intercourse (8% versus 14%; RR 0.57, 95% CI 0.38 to 0.87; 2P < 0.01). CONCLUSION: Two-stage repair of perineal trauma leaving the skin unsutured appears to reduce the likelihood of the perineum feeling different from before delivery, in addition to less pain and dyspareunia initially; there were no apparent disadvantages. Polyglactin 910 reduces dyspareunia long term, indicating that the short term benefits of this material over chromic catgut persist.
Adult↗
MR perfusion imaging reveals regions of hypoperfusion associated with aphasia and neglect.
OBJECTIVE: To evaluate diffusion-weighted imaging (DWI) and MR perfusion imaging (MRPI) as tools for identifying regions of infarct and hypoperfusion associated with aphasia and neglect in hyperacute stroke. Secondary goal: to establish a functional correlate of a radiologically defined "ischemic penumbra." METHODS: Forty subjects underwent DWI, MRPI, and standardized tests for lexical deficits or hemispatial neglect within 24 hours of stroke onset or progression. Ten patients had repeat DWI, MRPI, and cognitive testing after 3 days (in some cases after reperfusion therapy). Pearson correlations between error rate on cognitive testing and volume of abnormality on DWI versus MRPI were determined at each time period, and regions of hypoperfusion corresponding to specific cognitive deficits were identified. RESULTS: Error rate was more strongly correlated with volume of hypoperfused tissue on MRPI (r = 0.65 to 0.93; p < 0.01 to p < 0.0003) than with volume of lesion on DWI (r = 0.54 to 0.75; p = 0.14 to p < 0.01) for dominant and nondominant hemisphere stroke, at each time point. Forty-eight percent of aphasic patients and 67% of those with hemispatial neglect had either no infarct or only small subcortical infarct on DWI, but had focal cortical hypoperfusion. Patients who had successful reperfusion therapy showed resolution of the hypoperfused territory beyond the infarction on repeat MRPI and showed resolution of corresponding deficits. CONCLUSIONS: MRPI shows regions of hypoperfused cortex associated with lexical deficits or hemispatial neglect, even when DWI shows no infarct or only small subcortical infarct. MRPI-DWI mismatch indicates regions of functionally salvageable tissue.
Aphasia↗
Practice parameter: screening and diagnosis of autism: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Child Neurology Society [RETIRED].
Autism is a common disorder of childhood, affecting 1 in 500 children. Yet, it often remains unrecognized and undiagnosed until or after late preschool age because appropriate tools for routine developmental screening and screening specifically for autism have not been available. Early identification of children with autism and intensive, early intervention during the toddler and preschool years improves outcome for most young children with autism. This practice parameter reviews the available empirical evidence and gives specific recommendations for the identification of children with autism. This approach requires a dual process: 1) routine developmental surveillance and screening specifically for autism to be performed on all children to first identify those at risk for any type of atypical development, and to identify those specifically at risk for autism; and 2) to diagnose and evaluate autism, to differentiate autism from other developmental disorders.
Asperger Syndrome↗
Development of NR1, NR2A and NR2B mRNA in NR1 immunoreactive cells of rat visual cortex.
In cells marked for N-methyl-D-aspartate receptors (NMDARs), we studied the relationship between the sensitive period for monocular deprivation and the expression of rat NMDAR subunits, NR2A and NR2B. In the rat the sensitive period ends sometime after postnatal day 50 (P50). Previous studies of the development of these subunit mRNAs focused on animals prior to the end of the sensitive period and did not examine the visual cortex specifically. We used a monoclonal antibody to the NR1 subunit of the receptor to identify cells containing NMDARs. We then used in situ hybridization to label the same sections for NR2A or NR2B mRNA. In an additional experiment we labeled sections for NR1 mRNA to see if the developmental profile was similar at both the mRNA and protein level. We used five animals at each of four ages: P22, P30, P45 and P90. Staining for NR2B mRNA, but not for NR2A mRNA, decreased dramatically from P22 to P45. Staining for NR1 mRNA declined dramatically between P22 and P45 even though most cells remained strongly immunopositive for the NR1 protein during this time. This discrepancy suggests that significant NR1 regulation occurs after gene transcription. Because most of the decrease in NR1 mRNA and NR2B mRNA occurs by P30, transcriptional regulation of these subunits does not easily explain the loss of sensitivity to monocular deprivation, which occurs around P50. The changes are, in fact, more closely synchronized with the beginning of experience-dependent plasticity than with its end.
Age Factors↗
Postnatal development of NR1, NR2A and NR2B immunoreactivity in the visual cortex of the rat.
N-Methyl-D-aspartate receptors (NMDARs) are critically involved in some types of synaptic plasticity. The NMDAR subunits NR1, NR2A and NR2B are developmentally regulated, and it has been proposed that developmental changes in their expression may underlie developmental changes in cortical plasticity. Age-dependent change in cortical plasticity is most commonly measured by the monocular deprivation effect, which occurs during a critical period between P22 and P50 in the rat. Although the development of NMDAR subunits has been studied from birth through the fourth postnatal week, there is only meager information from older ages when visual plasticity ends. We hypothesized that there will be significant age-dependent change in expression of NR1, NR2A or NR2B between P22, when the cortex is plastic, and P90, when it is not. We applied specific antibodies recognizing NR1, NR2A and NR2B to the primary visual cortex at P14, P22, P30, P45 and P90. We found age-dependent changes in NR1-IR that were negatively correlated with changes in NR2A-IR; these subunits are not regulated in unison. In contrast, NR2A-IR and NR2B-IR were positively correlated. NR2A-IR and NR2B-IR both passed through a developmental minimum around P45, then recovered to approximately their P22 level. NR1-IR passed through a maximum at P45. There were no significant differences between P22 and P90. These results do not support the simple hypothesis that the loss of plasticity corresponds to a simple transition from juvenile levels of NMDAR subunit proteins to new adult levels. On the other hand, the results do confirm the hypothesis that there are significant changes in processing of NMDAR proteins during the time that plasticity is lost. How these changes of IR relate to synaptic transmission and plasticity needs to be clarified.
Animals↗
Geographic variation in allergic fungal rhinosinusitis.
Allergic fungal rhinosinusitis (AFRS) has a worldwide distribution. This survey of 20 otolaryngologic practices throughout the United States confirmed a variation in the frequency of AFRS relative to endoscopic sinus procedures performed for all other diagnoses. The highest incidence occurred in Memphis, Tennessee at 23%, with three other southern practices reporting a frequency of at least 10%. In the northern locations the frequency ranged from 0 to 4%. No correlation with mould counts was demonstrated, possibly because of incomplete mould data relative to most of the surgical locations.
Humans↗
Commentary: a neural systems perspective for improving behavioral treatments for autism.
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Autistic Disorder↗
The growth and metastasis of human, HER-2/neu-overexpressing tumor cell lines in male SCID mice.
HER-2/neu is overexpressed on a variety of human adenocarcinomas and overexpression has been associated with a poor prognosis. For this reason, HER-2 has become an attractive target for immunotherapy. To facilitate testing of anti-HER-2-monoclonal antibodies (MAbs) and immunotoxins (ITs), we have evaluated the in vivo growth and metastatic spread of three HER-2-overexpressing human breast cancer cell lines (BT474, MDA-MB-453 and HCC1954) and one ovarian cancer cell line (SKOV3.ip1) in pre-irradiated male SCID mice using subcutaneous (s.c.), intravenous (i.v.) and intraperitoneal (i.p.) routes of injection. All the cell lines tested grew as s.c. tumors and the growth of BT474 and MDA-MB-453 cells after s.c. injection was improved by co-inoculation with Matrigel. Metastases to the lungs were detectable by PCR or histopathology after s.c. injection of BT474 and to a much lesser extent after s.c. injection of HCC1954, MD-MB-453 and SKOV3.ip1 cells. I.p. injection of HCC1954 and SKOV3.ip1 cells produced fatal ascites while i.v. injection of SKOV3.ip1, but not BT474 or MDA-MB-453 cells, resulted in infiltration of lungs and death within 9-11 weeks.
Animals↗
Central nervous system dysfunction as the first manifestation of multiple organ dysfunction syndrome in stem cell transplant patients.
Development of CNS dysfunction in the setting of hematopoietic stem cell transplant (HSCT) has been previously shown to predict for subsequent second organ dysfunction and death. In this paper, we describe the characteristics of this isolated CNS dysfunction, and its relationship to multiple organ dysfunction syndrome (MODS) after HSCT. Twenty-one of 186 patients undergoing HSCT developed CNS dysfunction as their first organ dysfunction a mean of 22.8 +/- 0.9 days after the start of the preparative regimen. Compared with 137 patients who developed no organ dysfunction, patients presenting with CNS dysfunction were more likely to have undergone allogeneic HSCT (P = 0.001) and to have received a total body irradiation-based regimen (P = 0.001), and were less likely to have been transplanted for lymphoma (P = 0.008). Patients who developed CNS dysfunction were more likely to die than those with no organ dysfunction (P < 0. 001). Of the 21 patients who developed CNS dysfunction, 48% resolved their dysfunction by a mean of 4.6 days later without progression to second organ dysfunction, and 90% of these patients survived to day 100. Fifty-two percent of patients with CNS dysfunction progressed to second organ dysfunction (pulmonary or hepatic) a mean of 5.5 days later, and only 36% survived to day 100 (P = 0.02). The patients who progressed to second organ dysfunction and those who did not were not different in terms of type of HSCT (allogeneic vs autologous), stem cell source (blood vs bone marrow), age, diagnosis or preparative regimen. Development of CNS dysfunction in the setting of HSCT, as with other organ dysfunctions (such as hepatic veno-occlusive disease), probably represents an early manifestation of a systemic disorder predisposing for MODS, increasing the risk of transplant-related mortality. Early systemic therapies directed at modulating this systemic disorder are probably indicated. Bone Marrow Transplantation (2000) 25, 79-83.
Adult↗
Transcortical sensory aphasia: revisited and revised.
Transcortical sensory aphasia (TSA) is characterized by impaired auditory comprehension with intact repetition and fluent speech. We induced TSA transiently by electrical interference during routine cortical function mapping in six adult seizure patients. For each patient, TSA was associated with multiple posterior cortical sites, including the posterior superior and middle temporal gyri, in classical Wernicke's area. A number of TSA sites were immediately adjacent to sites where Wernicke's aphasia was elicited in the same patients. Phonological decoding of speech sounds was assessed by auditory syllable discrimination and found to be intact at all sites where TSA was induced. At a subset of electrode sites where the pattern of language deficits otherwise resembled TSA, naming and word reading remained intact. Language lateralization testing by intracarotid amobarbital injection showed no evidence of independent right hemisphere language. These results suggest that TSA may result from a one-way disruption between left hemisphere phonology and lexical-semantic processing.
Adult↗
Neural substrates of orthographic lexical access as demonstrated by functional brain imaging.
OBJECTIVE: To delineate regions involved in visual word recognition. BACKGROUND: The processes and regions involved in visual word recognition have been somewhat controversial for over 100 years. METHODS: This study used regional cerebral blood flow as assessed by functional magnetic resonance imaging to study normal subjects (N = 9) on an individual within-subject basis while they were actively engaged on-line in a visual lexical decision task. Standard analysis techniques were used for identifying regions of activation. RESULTS: Across subjects, the task activated a number of regions, including the occipital pole, lateral and basal occipitotemporal (including lingual and fusiform) regions, superior and middle temporal gyri, and supramarginal and angular gyri. Typically, these regions were activated bilaterally; when activation was unilateral, it was on the left. Some of the areas activated (e.g., inferior parietal regions) have not been previously reported to be involved in such types of processing by activation studies but have been implicated in lesion studies. CONCLUSIONS: These results broaden the areas known to be involved in visual word recognition. The bilateral activation associated with visual word recognition is in some respects analogous to the "what" system in visual recognition described in subhuman primates. In addition, the study raises several methodologic issues. The within-subject analysis showed variability in the specific regions activated when subsequently comparing across individuals, raising implications for future functional imaging studies.
Adult↗