RESUMEN

Background: Temporomandibular disorder (TMD) is a common condition that frequently transitions to chronic symptoms. Experimental pain models that mimic the symptoms of clinical TMD may be useful in understanding the mechanisms, and sex differences, present in this disorder. Here we aimed to comprehensively characterise the nature and time-course of pain, functional impairment and hyperalgesia induced by repeated intramuscular injection of nerve growth factor (NGF) into the masseter muscle, and to investigate sex differences in the NGF-induced pain experience. Methods: 94 healthy individuals participated in a longitudinal study with 30-day follow-up. NGF was injected into the right masseter muscle on Day 0 and Day 2. Participants attended laboratory sessions to assess pain (Numerical Rating Scale; NRS), functional limitation (mouth opening distance, Jaw Functional Limitation Scale; JFLS) and mechanical sensitization (pressure pain thresholds; PPTs) on Days 0, 2 and 5 and completed twice daily electronic pain dairies from Day 0 to day 30. Results: Peak pain averaged 2.0/10 (95 % CI: 1.6-2.4) at rest and 4.3/10 (95 % CI: 3.9-4.8) on chewing. Pain-free mouth opening distance reduced from 5.0 cm (95 % CI: 4.8-5.1 cm) on Day 0 to 3.7 cm (95 % CI: 3.5-3.9 cm) on Day 5. The greatest reduction in PPTs was observed over the masseter muscle. Females experienced higher pain, greater functional impairment, and greater sensitivity to mechanical stimuli than males. Conclusion: Intramuscular injection of NGF is a useful model with which to explore the mechanisms, and sex differences, present in clinical TMD.

Asunto(s)

RESUMEN

INTRODUCTION: Compared with young children who have acute lymphoblastic leukaemia (ALL), adolescents with ALL have unfavourable disease profiles and worse survival. However, limited data are available regarding the characteristics and outcomes of adolescents with ALL who underwent treatment in clinical trials. The aim of this study was to investigate the causes of treatment failure in adolescents with ALL. METHODS: We retrospectively analysed the outcomes of 711 children with ALL, aged 1-18 years, who were enrolled in five clinical trials of paediatric ALL treatment between 1993 and 2015. RESULTS: Among the 711 children with ALL, 530 were young children (1-9 years at diagnosis) and 181 were adolescents (including 136 younger adolescents [10-14 years] and 45 older adolescents [15-18 years]). Compared with young children who had ALL, adolescents with ALL were less likely to have favourable genetic features and more likely to demonstrate poor early response to treatment. The 10-year overall survival and event-free survival rates were significantly lower among adolescents than among young children (77.9% vs 87.6%, P=0.0003; 69.7% vs 76.5%, P=0.0117). There were no significant differences in the 10-year cumulative incidence of relapse, but the 10-year cumulative incidence of treatment-related death (TRD) was significantly greater among adolescents (7.2%) than among young children (2.3%; P=0.002). Multivariable analysis showed that both younger and older adolescents (vs young children) had worse survival and greater incidence of TRD. CONCLUSION: Adolescents with ALL had worse survival because they experienced a greater incidence of TRD. There is a need to investigate optimal treatment adjustments and novel targeted agents to achieve better survival rates (without excessive toxicity) among adolescents with ALL.

Asunto(s)

RESUMEN

Clinical use of heated, high-flow nasal cannula (HFNC) for noninvasive respiratory support is increasing and may have a therapeutic role in stabilizing the upper airway in obstructive sleep apnea (OSA). However, physiological mechanisms by which HFNC therapy may improve upper airway function and effects of different temperature modes are unclear. Accordingly, this study aimed to determine effects of incremental flows and temperature modes (heated and nonheated) of HFNC on upper airway muscle activity (genioglossus), pharyngeal airway pressure, breathing parameters, and perceived comfort. Six participants (2 females, aged 35 ± 14 yr) were studied during wakefulness in the supine position and received HFNC at variable flows (0-60 L/min) during heated (37°C) and nonheated (21°C) modes. Breathing parameters via calibrated Respitrace inductance bands (chest and abdomen), upper airway pressures via airway transducers, and genioglossus muscle activity via intramuscular bipolar fine wire electrodes were measured. Comfort levels during HFNC were quantified using a visual analog scale. Increasing HFNC flows did not increase genioglossus muscle activation despite increased negative epiglottic pressure swings (P = 0.009). HFNC provided ∼7 cmH2O positive airway pressure at 60 L/min in nonheated and heated modes. In addition, increasing the magnitude of HFNC flow reduced breathing frequency (P = 0.045), increased expiratory time (P = 0.040), increased peak inspiratory flow (P = 0.002), and increased discomfort (P = 0.004). Greater discomfort occurred at higher flows in the nonheated versus the heated mode (P = 0.034). These findings provide novel insight into key physiological changes that occur with HFNC for respiratory support and indicate that the primary mechanism for improved upper airway stability is positive airway pressure, not increased pharyngeal muscle activity.NEW & NOTEWORTHY This study evaluated upper airway muscle function, breathing, and comfort across different HFNC flows and temperatures. There were no increases in genioglossus muscle activity at higher flows despite greater negative epiglottic pressure swings. Increasing negative pressure swings was associated with increasing discomfort in the nonheated mode. HFNC was associated with ∼7 cmH2O increase in positive airway pressure, which may be the primary mechanism for upper airway stability with HFNC rather than increases in pharyngeal muscle activity.

Asunto(s)

RESUMEN

A 7-year-old male with Stage 4 neuroblastoma was treated with chemotherapy and autologous hematopoietic stem cell transplantation (HSCT), resulting in partial response with residual bone and marrow disease. He proceeded to haploidentical-HSCT with his mother as donor and achieved remission. The patient developed marrow relapse 2 years after haploidentical-HSCT with cytopenia and dropping donor chimerism. Donor lymphocyte infusion (DLI) using mother's whole blood was given resulting in clearance of marrow disease, resolution of cytopenia, and full donor chimerism. This is the first report of successful treatment for neuroblastoma relapse after haploidentical-HSCT using DLI alone, supporting the role of adoptive cell therapy post-HSCT in neuroblastoma.

Asunto(s)

RESUMEN

UNLABELLED: Undifferentiated nasopharyngeal carcinoma (NPC) has a 100% association with Epstein-Barr virus (EBV). However, only three EBV genomes isolated from NPC patients have been sequenced to date, and the role of EBV genomic variations in the pathogenesis of NPC is unclear. We sought to obtain the sequences of EBV genomes in multiple NPC biopsy specimens in the same geographic location in order to reveal their sequence diversity. Three published EBV (B95-8, C666-1, and HKNPC1) genomes were first resequenced using the sequencing workflow of target enrichment of EBV DNA by hybridization, followed by next-generation sequencing, de novo assembly, and joining of contigs by Sanger sequencing. The sequences of eight NPC biopsy specimen-derived EBV (NPC-EBV) genomes, designated HKNPC2 to HKNPC9, were then determined. They harbored 1,736 variations in total, including 1,601 substitutions, 64 insertions, and 71 deletions, compared to the reference EBV. Furthermore, genes encoding latent, early lytic, and tegument proteins and glycoproteins were found to contain nonsynonymous mutations of potential biological significance. Phylogenetic analysis showed that the HKNPC6 and -7 genomes, which were isolated from tumor biopsy specimens of advanced metastatic NPC cases, were distinct from the other six NPC-EBV genomes, suggesting the presence of at least two parental lineages of EBV among the NPC-EBV genomes. In conclusion, much greater sequence diversity among EBV isolates derived from NPC biopsy specimens is demonstrated on a whole-genome level through a complete sequencing workflow. Large-scale sequencing and comparison of EBV genomes isolated from NPC and normal subjects should be performed to assess whether EBV genomic variations contribute to NPC pathogenesis. IMPORTANCE: This study established a sequencing workflow from EBV DNA capture and sequencing to de novo assembly and contig joining. We reported eight newly sequenced EBV genomes isolated from primary NPC biopsy specimens and revealed the sequence diversity on a whole-genome level among these EBV isolates. At least two lineages of EBV strains are observed, and recombination among these lineages is inferred. Our study has demonstrated the value of, and provided a platform for, genome sequencing of EBV.

Asunto(s)

RESUMEN

Because of the rarity of dural sinus thrombosis in children with polycythaemia vera (PV), the options for diagnosis and treatment remain elusive. A 12-year-old girl was admitted with dural sinus thrombosis associated with PV, diagnosed by magnetic resonance venography. She was managed with interventional endovascular thrombolectomy and venoplasty, phlebotomy, hydroxyurea, low molecular weight heparin, and aspirin followed by warfarin. She made a good recovery without residual neurological deficit. This case highlights the importance of diagnosis and appropriate intervention with multi-modality treatments in patients with PV and thrombosis.

Asunto(s)

RESUMEN

OBJECTIVE: To investigate age trends, sex differences, and splitting of alpha peaks of the EEG spectrum in the healthy population. METHODS: An automated multi-site algorithm was used to parametrize the alpha rhythm in 1498 healthy subjects aged 6-86 years. Alpha peaks identified from multiple electrode sites were organized into clusters of similar frequencies whose sex differences and age trends were investigated. RESULTS: Significant age-related trends were observed for frequency, position, and amplitude of dominant alpha peaks. Occipital sites had alpha clusters of higher average frequency, higher power, and greater presence across the scalp. Frequency and power differences were found between the sexes. CONCLUSION: Observed increases in alpha frequency in children and decreases in the elderly were consistent with those from earlier studies. A large fraction of participants (≈ 44%) showed multiple distinct alpha rhythm thus investigations which only examine the alpha frequency with the highest peak power can produce misleading results. The strong dependence of alpha frequency on age and anterior-posterior position indicates use of a fixed alpha frequency band is insufficient to capture the full characteristics of the alpha rhythm. SIGNIFICANCE: This study establishes alpha rhythm parameter ranges (including power and frequency) in the healthy population, and quantifies the variation in alpha frequency across the scalp. The automated characterization enables objective evaluations of alpha band activities over large samples. These findings are potentially useful in testing theories of alpha generation, where splitting of the alpha rhythm has been theoretically predicted to occur in individuals with large differences in axon length between anterior and posterior corticothalamic loops.

Asunto(s)

RESUMEN

OBJECTIVE: To investigate age-associated changes in physiologically-based EEG spectral parameters in the healthy population. METHODS: Eyes-closed EEG spectra of 1498 healthy subjects aged 6-86 years were fitted to a mean-field model of thalamocortical dynamics in a cross-sectional study. Parameters were synaptodendritic rates, cortical wave decay rates, connection strengths (gains), axonal delays for thalamocortical loops, and power normalizations. Age trends were approximated using smooth asymptotically linear functions with a single turning point. We also considered sex differences and relationships between model parameters and traditional quantitative EEG measures. RESULTS: The cross-sectional data suggest that changes tend to be most rapid in childhood, generally leveling off at age 15-20 years. Most gains decrease in magnitude with age, as does power normalization. Axonal and dendritic delays decrease in childhood and then increase. Axonal delays and gains show small but significant sex differences. CONCLUSIONS: Mean-field brain modeling allows interpretation of age-associated EEG trends in terms of physiological processes, including the growth and regression of white matter, influencing axonal delays, and the establishment and pruning of synaptic connections, influencing gains. SIGNIFICANCE: This study demonstrates the feasibility of inverse modeling of EEG spectra as a noninvasive method for investigating large-scale corticothalamic dynamics, and provides a basis for future comparisons.

Asunto(s)

RESUMEN

In this cross-sectional study, we compared the quality of life (QOL) in transfusion-dependent thalassemic patients who survived matched sibling hematopoietic SCT (HSCT, n=24) with patients treated conventionally with transfusion and iron chelation (n=74). WHOQOL-BREF(HK) and PedsQL questionnaires were administered to patients aged >18 years and 5-12 years, respectively. Patients aged 12-18 years received both questionnaires. WHOQOL-BREF(HK) revealed post transplant patients rated overall health better than those treated conventionally (score 3.67 vs 3.06, P=0.01). They are less dependent on medical aids (3.87 vs 2.96, P=0.006), having higher activity level (4.00 vs 3.36, P=0.026) and better personal relationships (4.13 vs 3.69, P=0.014). Physical health domain score was better (75.20 vs 63.94, P=0.007). These differences remained significant after adjustment for comorbidities. PedsQL revealed post transplant patients rated better for running (3.53 vs 2.72, P=0.001) and sports (3.20 vs 2.64, P=0.038), even after adjustment for comorbidities, but were less satisfied for school absence to attend hospital (2.53 vs 3.29, P=0.03). Post transplant patients were significantly more likely to consider marriage (100 vs 75.7%, P=0.033), but not childbearing (66.7 vs 51.4%, P=0.28). In conclusion, transplanted thalassemic patients enjoy better QOL, mainly in physical health, compared with conventionally treated patients. This information is important to patients considering HSCT.

Asunto(s)

RESUMEN

The identification of alpha rhythm in the human electroencephalogram (EEG) is generally a laborious task involving visual inspection of the spectrum. Moreover the occurrence of multiple alpha rhythms is often overlooked. This paper seeks to automate the process of identifying alpha peaks and quantifying their frequency, amplitude and width as a function of position on the scalp. Experimental EEG was fitted with parameterized spectra spanning the alpha range, with results categorized by multi-site criteria into three distinct classes: no distinguishable alpha peak, a single alpha peak, and two alpha peaks. The technique avoids visual bias, integrates spatial information, and is automated. We show that multiple alpha peaks are a common feature of many spectra.

Asunto(s)

RESUMEN

A cohort of 138 children with 144 hematopoietic stem cell transplantation (HSCT) performed in 1997-2006 were analyzed to evaluate risk factors and mortality predictors of hepatic veno-occlusive disease (VOD). Nineteen patients (13.2%) developed VOD (nine boys, median age 3.5 years) at 1-21 days after HSCT (median 13 days). Age < or =2 years at transplant (odds ratio (OR)=5.25, P=0.011), BU-CY conditioning (OR=5.16, P=0.001), thalassemia major (OR=3.97, P=0.015), platelet engraftment beyond day +21 (OR=8.67, P=0.025) were univariate risk factors for VOD. The first two remained significant in multivariate regression. Seven patients (36.8%) with VOD died, at a median of 44 days post transplant (range, 30-421 days). The 5-year survival was 62%. All surviving patients had normal liver function on follow-up at 0.5-9 years. Patients with VOD had higher 100-day mortality (16.3 vs 9.6%, P=0.024). Mortality predictors included donors other than autologous or matched sibling (hazard ratio (HR)=23.6, P=0.006), hepatic and cutaneous GVHD (HR=8.15, P=0.038), maximal weight gain >9% (HR=6.81, P=0.023), pleural effusion, intensive care unit admission, peak bilirubin >300 micromol l(-1) (HR=13.6, P=0.016), day +21 bilirubin >200 micromol l(-1) (HR=33.9, P=0.001), and rise of bilirubin >15 micromol l(-1) per day within the first week (HR=19.8, P=0.006). Mortality was substantially higher if >3 predictors were present (HR=33.9, P=0.001). Meticulous monitoring in high-risk patients and early treatment should be considered before VOD progresses beyond salvage.

Asunto(s)

RESUMEN

Chemokines play a major role in leukocyte recruitment during the formation of tuberculous granulomas. We studied the association between genetic polymorphisms of three chemokines, monocyte chemoattractant protein-1 (MCP-1), RANTES (regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1alpha (MIP-1alpha), and tuberculosis (TB). The distribution of five functionally significant single-nucleotide polymorphisms (SNPs), MCP-1 -2518A/G, RANTES -403G/A, -28C/G and In1.1T/C as well as MIP-1alpha +459C/T was not found to be different between patients with TB and healthy control subjects of the Hong Kong Chinese population. However, differences in linkage disequilibrium (LD) of the SNPs of RANTES and in distribution of the haplotypes of RANTES between patients with TB and healthy controls (P<0.0001) were found. Two risk haplotypes of RANTES, A-C-T and G-C-C, at positions -403, -28 and In1.1, respectively, were identified. Furthermore, combining the genotypes of RANTES -403 and In1.1, two diplotypes GA/TT (P<0.001) and GG/TC (P<0.0001) showed strong association with TB. Our findings support the association between RANTES functional polymorphisms and TB.

Asunto(s)

RESUMEN

Interferon gamma (IFN-gamma) and interleukin 10 (IL-10) are believed to play opposing roles in host immunity against mycobacterial infection. IFN-gamma activates macrophages, while IL-10 downregulates the expression of T helper type 1 cytokines, MHC class II antigens and costimulatory molecules on macrophages. Associations of IFN-gamma -179 (G/T), +874 (A/T), +875 miscrosatellite CA repeats and +4766 (C/T), and IL-10 -1082 (A/G), -819 (C/T) and -592 (C/A) with tuberculosis (TB) were investigated in 385 HIV-negative patients and 451 controls in a Hong Kong Chinese population. The frequency of a low IFN-gamma-producing +874 A/A genotype was significantly over-represented in the patient group (P<0.001, OR=3.79, 95% CI=1.93-7.45). We identified 10 alleles in the IFN-gamma CA repeats and observed a significant difference in allele frequency distribution between patients and controls (P<0.001). By grouping alleles into 12 and non-12 CA repeats, the non-12/non-12 genotype yielded a similar significant result (P<0.001, OR=4.56, 95% CI=2.21-9.43) as observed in +874 A/A genotype. Weak associations of the IL-10 GCC/- genotype (P=0.04) and the low IFN-gamma-producing A/A genotype (P=0.06) with TB relapse/extrapulmonary cases were found. This study suggests the possible role of interferon gamma in TB susceptibility.

Asunto(s)

RESUMEN

OBJECTIVE: To delineate the clinical behaviour of chronic benign neutropenia in Chinese children in Hong Kong. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS: All infants and children with absolute neutrophil count of 1.5 x 10(9) /L or lower for more than 3 months. MAIN OUTCOME MEASURES: Development of significant infection, and achievement of remission. RESULTS: Twenty-four children with chronic benign neutropenia were identified between 1992 and 2001. Their median age of diagnosis was 9 months. The mean (standard deviation) initial absolute neutrophil count was 0.28 x 10(9) /L (0.24 x 10(9) /L). Twenty-three patients presented with infection. Of the 19 patients tested, four (21%) were positive for anti-neutrophil antibodies. Bone marrow examination was performed in 17 patients: nine had normal results, but six showed evidence of peripheral consumption, one showed late maturation arrest at band stage, and one showed phagocytosis of myeloid cells by histiocytes. The overall hospitalised infection rate was 51.6 episodes per 1000 patient-months. Ten percent of cases were considered 'significant' infections and required hospital admission with either surgical intervention or intravenous therapy (antibiotics or fluid replacement). In the first year of diagnosis, more than 80% of patients had their lowest absolute neutrophil count (mean, 0.16 x 10(9) /L; standard deviation, 0.11 x 10(9) /L). Granulocyte-colony stimulating factor was used to treat three patients and induced transient elevation of absolute neutrophil count in all three. The projected remission rate was 55.4% at 3 years. Even for those with persistent disease, there was significant recovery in absolute neutrophil count to a mean of 0.5 x 10(9) /L (P<0.01). CONCLUSIONS: Patients with chronic benign neutropenia experienced a relatively benign clinical course regardless of their remission status. Only a small proportion of patients developed significant infections. A multi-centre prospective study may help identify predictive factors of remission.

Asunto(s)

RESUMEN

OBJECTIVES: To compare and contrast clinical characteristics and outcomes of hepatoblastoma or hepatocellular carcinoma in paediatric patients. DESIGN: Retrospective study. SETTING: University teaching hospital, Hong Kong. PATIENTS AND METHODS: Medical records of 22 paediatric patients with hepatoblastoma (n=11) or hepatocellular carcinoma (n=11) admitted to Queen Mary Hospital between 1989 and 2000 were reviewed. Data gathered included demographic data, results of liver function tests, hepatitis A, B, and C titres, and alpha-foetoprotein levels, and imaging studies including chest X-ray, ultrasound study, computed tomography scan, and magnetic resonance imaging/hepatic angiogram for tumour staging and resectability. RESULTS: The mean age of patients with hepatoblastoma was 18 months (range, 5 months to 3 years), while that of patients with hepatocellular carcinoma was 10.2 years (range, 2 to 16 years). Females predominated in the hepatoblastoma group (female:male, 8:3) and males in the hepatocellular carcinoma group (male:female, 10:1). None of the patients with hepatoblastoma were hepatitis B surface antigen positive, in contrast to 64% of the hepatocellular carcinoma group. Only 45% of the hepatocellular carcinomas were resectable at presentation and this figure remained unchanged following chemotherapy. A total of 91% of hepatoblastomas were resectable, four at presentation, and a further six after chemotherapy. Tumour rupture was more common in patients with hepatoblastoma than in those with hepatocellular carcinoma (36% versus 9% of cases, respectively). Mortality rates were considerably higher among the hepatocellular carcinoma group than the hepatoblastoma group in this series. CONCLUSION: Childhood hepatoblastoma and hepatocellular carcinoma differ with respect to age and tumour stage at presentation, hepatatis B surface antigen status, tendency to rupture, chemosensitivity, and prognosis.

Asunto(s)

Asunto(s)

RESUMEN

A recently developed, physiologically based continuum model of corticothalamic electrodynamics is used to derive the theoretical form of the electroencephalographic wave-number spectrum and its projection onto a one-dimensional recording array. The projected spectrum is found to consist of a plateau followed by regions of power-law decrease with various exponents, which are dependent on both model parameters and temporal frequency. The theoretical spectrum is compared with experimental results obtained in other studies, showing good agreement. The model provides a framework for understanding the nature of the spatial power spectrum by linking the underlying physiology with the large-scale dynamics of the brain.

Asunto(s)

Asunto(s)

RESUMEN

Several mechanisms of immune escape might be in operation in Epstein-Barr virus (EBV)-associated nasal NK/T-cell lymphoma. We have previously shown the downregulation of the immunogenic EBV nuclear antigens by alternative promoter usage and the preferential selection of the deletion genotype of latent membrane protein 1 in nasal lymphoma. To understand further the strategies used for immune escape by this tumor, we examined by immunohistochemistry HLA class I expression in 15 cases using frozen sections, along with beta(2)-microglobulin and transporter associated with antigen processing 1 (TAP1) expression in 39 cases using paraffin sections. All nasal NK/T-cell lymphomas showed positive staining for HLA class I, beta(2)-microglobulin and TAP1 on most tumor cells, except for two cases (5%) in which most of the tumor cells lacked beta(2)-microglobulin staining. We next immunostained for interleukin-10 on frozen sections in 13 cases, all of which showed strong expression by most tumor cells. Transcription of human interleukin-10 but not EBV BCRF1 (viral interleukin-10) was identified by reverse transcriptase-polymerase chain reaction in these nasal NK/T-cell lymphomas. Overall, our data suggest that global downregulation of HLA class I or TAP1 rarely accounts for the ability of nasal NK/T-cell lymphoma to evade immunosurveillance and that other immune escape mechanisms may be operating in nasal NK/T-cell lymphoma, such as production of interleukin-10 to suppress the local immune response.

Asunto(s)