Epidemiology of leukaemia and lymphoma in children and young adults from the north of England, 1990–2002

AimWe aimed to describe and contrast the epidemiology of haematological malignancies among 0–14 and 15–24-year-olds in northern England from 1990 to 2002 and compare clinical trial entry by age group.Patients and methodsIncidence rates were examined by age, sex and period of diagnosis and differences were tested using Poisson regression. Differences and trends in survival were assessed using Cox regression.Results1680 subjects were included comprising 948 leukaemias and 732 lymphomas. Incidence rates for acute lymphoblastic leukaemia were significantly higher for 0–14 compared to 15–24-year-olds, whilst Hodgkin lymphoma showed the reverse. No significant changes in incidence were observed. 60% of leukaemia patients aged 15–24 years entered trials compared to 92% of 0–14-year-olds. Survival rates were significantly lower and improved less markedly over time for 15–24 compared to 0–14-year-olds, particularly for leukaemia.ConclusionsTrial accrual rates need to be improved amongst 15–24-year-olds and a more structured follow-up approach adopted for this unique population.     

Human cortical responses to the speech envelope

OBJECTIVE: To evaluate the response of the human auditory cortex to the temporal amplitude-envelope of speech. Responses to the speech envelope could be useful for validating the neural encoding of intelligible speech, particularly during hearing aid fittings--because hearing aid gain and compression characteristics for ongoing speech should more closely resemble real world performance than for isolated brief syllables. DESIGN: The speech envelope comprises energy changes corresponding to phonemic and syllabic transitions. Envelope frequencies between 2 and 20 Hz are important for speech intelligibility. Human event-related potentials were recorded to six different sentences and the sources of these potentials in the auditory cortex were determined. To improve the signal to noise ratio over ongoing electroencephalographic recordings, we averaged the responses over multiple presentations, and derived source waveforms from multichannel scalp recordings. Source analysis led to bilateral, symmetrical, vertical, and horizontal dipoles in the posterior auditory cortices. The source waveforms were then cross-correlated with the low frequency log-envelopes of the sentences. The significance and latency of the maximum correlation for each sentence demonstrated the presence and latency of the brain's response. The source waveforms were also cross-correlated with a simple model based on a series of overlapping transient responses to stimulus change (the derivative of the log-envelope). RESULTS: Correlations between the log-envelope and vertical dipole source waveforms were significant for all sentences and for all but one of the participants (mean r = 0.35), at an average delay of 175 (left) to 180 (right) msec. Correlations between the transient response model (P1 at 68 msec, N1 at 124 msec, and P2 at 208 msec) and the vertical dipole source waveforms were detected for all sentences and all participants (mean r = 0.30), at an average delay of 6 (right) to 10 (left) msec. CONCLUSIONS: These results show that the human auditory cortex either directly follows the speech envelope or consistently reacts to changes in this envelope. The delay between the envelope and the response is approximately 180 msec.     

Envelope and spectral frequency-following responses to vowel sounds

Frequency-following responses (FFRs) were recorded to two naturally produced vowels (/a/ and /i/) in normal hearing subjects. A digitally implemented Fourier analyzer was used to measure response amplitude at the fundamental frequency and at 23 higher harmonics. Response components related to the stimulus envelope ("envelope FFR") were distinguished from components related to the stimulus spectrum ("spectral FFR") by adding or subtracting responses to opposite polarity stimuli. Significant envelope FFRs were detected at the fundamental frequency of both vowels, for all of the subjects. Significant spectral FFRs were detected at harmonics close to formant peaks, and at harmonics corresponding to cochlear intermodulation distortion products, but these were not significant in all subjects, and were not detected above 1500 Hz. These findings indicate that speech-evoked FFRs follow both the glottal pitch envelope as well as spectral stimulus components.     

Correlates of eye blinking as determined by synthetic aperture magnetometry.

OBJECTIVE: To evaluate the spatiotemporal characteristics of ocular and cerebral current sources during voluntary eyeblinking. METHODS: Whole-head magnetoencephalographic (MEG) recordings were acquired during voluntary blinking in eight healthy adults and analysed using synthetic aperture magnetometry (SAM). RESULTS: Fronto-temporal MEG sensors showed a large slow wave lasting approximately 400 ms and a small burst of activity with frequencies above 30 Hz at the initiation of the blink. Group maps of blink-related oscillatory activity at frequencies between 1-18 Hz and 32-64 Hz showed increased activity in and around the orbits during the 400 ms following blink onset. Increased oscillatory activity occurred in occipital regions 200 ms after blink onset at frequencies between 18 and 64 Hz. CONCLUSIONS: Blink-related MEG signals are recorded in the regions of the eyes and in the occipital cortex. The anterior activation is likely a combination of muscle contraction and eyelid currents. Occipital activation likely represents neural processes concerned with re-establishing the visual image after transient ocular occlusion. SIGNIFICANCE: The possibility of eyeblink-related fields should be considered when interpreting frontal and occipital source activities during SAM analyses.     

Diffuse intrinsic pontine glioma treated with prolonged temozolomide and radiotherapy – Results of a United Kingdom phase II trial (CNS 2007 04)

Diffuse intrinsic pontine glioma (DIPG) has a dismal prognosis with no chemotherapy regimen so far resulting in any significant improvement over standard radiotherapy. In this trial, a prolonged regimen (21/28 d) of temozolomide was studied with the aim of overcoming O⁶-methylguanine methyltransferase (MGMT) mediated resistance.Forty-three patients with a defined clinico-radiological diagnosis of DIPG received radiotherapy and concomitant temozolomide (75 mg/m²) after which up to 12 courses of 21 d of adjuvant temozolomide (75–100 mg/m²) were given 4 weekly. The trial used a 2-stage design and passed interim analysis.At diagnosis median age was 8 years (2–20 years), 81% had cranial nerve abnormalities, 76% ataxia and 57% long tract signs. Median Karnofsky/Lansky score was 80 (10–100). Patients received a median of three courses of adjuvant temozolomide, five received all 12 courses and seven did not start adjuvant treatment. Three patients were withdrawn from study treatment due to haematological toxicity and 10 had a dose reduction. No other significant toxicity related to temozolomide was noted. Overall survival (OS) (95% confidence interval (CI)) was 56% (40%, 69%) at 9 months, 35% (21%, 49%) at 1 year and 17% (7%, 30%) at 2 years. Median survival was 9.5 months (range 7.5–11.4 months). There were five 2-year survivors with a median age of 13.6 years at diagnosis.This trial demonstrated no survival benefit of the addition of dose dense temozolomide, to standard radiotherapy in children with classical DIPG. However, a subgroup of adolescent DIPG patients did have a prolonged survival, which needs further exploration.     

The ophthalmic natural history of paediatric craniopharyngioma: a long-term review

We present our experience over the long-term of monitoring of visual function in children with craniopharyngioma. Our study involves an analysis of all paediatric patients with craniopharyngioma younger than 16 at the time of diagnosis and represents a series of predominantly sub-totally resected tumours. Visual data, of multiple modality, of the paediatric patients was collected. Twenty patients were surveyed. Poor prognostic indicators of the visual outcome and rate of recurrence were assessed. Severe visual loss and papilledema at the time of diagnosis were more common in children under the age of 6. In our study visual signs, tumour calcification and optic disc atrophy at presentation are predictors of poor visual outcome with the first two applying only in children younger than 6. In contrast with previous reports, preoperative visual field (VF) defects and type of surgery were not documented as prognostic indicators of poor postoperative visual acuity (VA) and VF. Contrary to previous reports calcification at diagnosis, type of surgery and preoperative VF defects were not found to be associated with tumour recurrence. Local recurrence is common. Younger age at presentation is associated with a tendency to recur. Magnetic resonance imaging (MRI) remains the recommended means of follow-up in patients with craniopharyngioma.     

Attenuation of the 40-Hertz Auditory Steady State Response by Propofol Involves the Cortical and Subcortical Generators

Background: The 40-Hz auditory steady state response (40-Hz ASSR) provides a reliable marker of anesthetic-induced unconsciousness. Brain electric source analysis indicates that the 40-Hz ASSR arises from cortical and subcortical generators. The authors used source analysis to assess the effect of propofol anesthesia on the cerebral generators of the 40-Hz ASSR. They also examined the effect of propofol on two auditory evoked potentials of cortical origin: the N1 and the sustained potential.

Methods: Eleven healthy human volunteers were anesthetized with propofol given in target-concentration mode at the minimal concentration causing unconsciousness. The 40-Hz ASSR was recorded before, during, and after anesthesia. The source model consisted of five concurrently active generator dipoles: two in the contralateral auditory cortex (one tangentially oriented, one radially oriented), two in the ipsilateral auditory cortex (same orientations), and one in the midline brainstem.

Results: During anesthesia, the strength of the cortical and brainstem dipoles was reduced to the same extent (to 54% of baseline for the four cortical dipoles pooled vs. 53% for the brainstem dipole). Dipole strength during anesthesia was significantly less (P < 0.01) than during baseline and recovery for both cortical and brainstem dipoles. The N1 and sustained potential were no longer recordable during anesthesia.     

Banff criteria as predictors of outcome following acute renal allograft rejection.

BACKGROUND: The Banff classification of renal allograft rejection grades acute tubulointerstitial rejection (AIR) by severity of tubulitis and acute vascular rejection (AVR) by severity of arteritis. The intensity of tubulitis has not, however, been demonstrated to be of prognostic value and other features such as glomerulitis and eosinophil infiltration are of uncertain significance. This study was performed in order to determine the clinical value of this pathological classification. METHODS: Banff criteria were correlated with outcome in 134 consecutive graft recipients transplanted in our unit over a 3-year period (1994 1996) who experienced at least one biopsy-confirmed acute rejection episode. Of 197 biopsies performed for the diagnosis of rejection, 177 contained at least one artery and were suitable for Banff grading. Tissue eosinophil counts were available for 101 biopsies. Clinical severity of rejection was classified as mild (fully responsive to pulse steroid therapy), moderate (partially steroid responsive) and severe (steroid unresponsive/requiring ATG therapy). RESULTS: Graft failure ensued in 18 of 58 patients with AVR compared with 10 of 65 patients with AIR (P= < 0.05). Clinical severity of rejection correlated with the presence of arteritis, but not severity of tubulitis; rejections graded I, IIA and IIB according to the Banff' 93 classification were clinically severe in 3/68 (4%), 2/28 (7%) and 15/67 (22%) respectively (P= <0.05). The presence of glomerulitis showed no correlation with clinical severity or graft loss. Tissue eosinophilia (>10 eosinophils/mm2) was present in 18 of 33 patients who had at least one episode of AVR (v1/2), compared with 11 of 45 patients who suffered only AIR (P= <0.02). CONCLUSIONS: We conclude that: arteritis, but not severe tubulitis or glomerulitis, is an adverse prognostic factor in acute rejection and that tissue eosinophilia is associated with vascular rejection. Our findings support the 1997 revision of the Banff classification, replacing grades with types of acute rejection.