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1.
Occup Med (Lond) ; 74(3): 242-250, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38722211

ABSTRACT

BACKGROUND: Mental ill health has a high economic impact on society and employers. National and international policy advocates line manager (LM) training in mental health as a key intervention, but little is known about employer training provisions. AIMS: To explore the prevalence and characteristics of organizations that offer LM training in mental health. METHODS: Secondary analysis of existing longitudinal anonymised organizational-level survey data derived from computer-assisted telephone interview surveys collected in four waves (2020:1900 firms, 2021:1551, 2022:1904, 2023:1902) in England, before, during and after a global pandemic. RESULTS: The proportion of organizations offering LM training in mental health increased pre- to post-pandemic (2020:50%, 2023:59%) but 41% do not currently provide it. Logistic regression confirmed that LM training is more likely to be offered by large-sized enterprises, organizations with a larger proportion of employees who are younger (aged 25-49), female, disabled and from ethnic minority communities. Sector patterns were inconsistent, but in 2023, organizations from the 'Hospitality' and 'Business Services' sectors were more likely to provide LM training than other sectors. CONCLUSIONS: Continued efforts are needed to increase the proportion of employers offering LM training in mental health, particularly small- to medium-sized enterprises, and organizations with predominantly male, White and/or older workforces.


Subject(s)
Mental Health , Humans , Female , Adult , Male , Middle Aged , England , COVID-19/epidemiology , Occupational Health , Surveys and Questionnaires
2.
Child Care Health Dev ; 40(4): 515-24, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23952538

ABSTRACT

BACKGROUND: Past research focused on the effects of raising a child with autism spectrum disorder on families. However, most research examined parents' perspectives rather than siblings' perspectives. Therefore, the purpose of this qualitative descriptive design was to use photo elicitation to capture perspectives of siblings living with a child with autism spectrum disorder. METHODS: Fourteen siblings (nine male) of 13 children with autism spectrum disorder received disposable cameras with 24-27 colour exposures, and were asked to photograph what was important to them within 2 weeks. After developing snapshots, investigators interviewed siblings about their photographs, and used open, axial and selective coding to determine photograph categories and subcategories. RESULTS: Two major categories were found: people (family members, non-family members) and non-people (personal items/objects, animals, buildings, scenery). Interviews about photographs reflected experiences siblings had with people/non-people in the snapshots and their normal everyday activities. Most photographs revealed family life and activities any sibling would experience whether or not they lived in a family raising a child with autism spectrum disorder. CONCLUSIONS: Photo elicitation facilitates communication between children and health-care professionals, and provides information about living with a child with autism spectrum disorder from the sibling's perspective. This information contributes to our knowledge base and allows development of specific intervention plans for siblings of these children.


Subject(s)
Child Development Disorders, Pervasive/psychology , Photography , Sibling Relations , Siblings/psychology , Symbolism , Adaptation, Psychological , Adolescent , Age Factors , Attitude to Health , Child , Communication , Family Health , Family Relations , Female , Humans , Male , Qualitative Research , Research Design , Stress, Psychological/psychology
3.
Child Care Health Dev ; 35(3): 330-9, 2009 May.
Article in English | MEDLINE | ID: mdl-19250255

ABSTRACT

BACKGROUND: Youth with type 1 diabetes cope with a variety of stressors related to daily life and disease management. While previous studies have focused on diabetes-related stressors, little research has examined daily stressors. METHODS: In this qualitative descriptive study, daily stressors and coping responses of 19 children and 33 adolescents with type 1 diabetes (65% are female) were investigated. Participants recorded their own stressors and coping responses in daily diaries for 2-3 weeks. RESULTS: Five broad themes of daily stressors emerged: people, self, context, no stressor and ambiguous. Coping responses included three general themes: submission, personal responsibility and ambiguous. Younger children reported more stressors related to friends/peers and siblings (people), and adolescents described more stressors related to self, parents (people) and school (context). Younger children used more coping that involved choosing an alternate activity, helping others and an emotional response (taking personal responsibility), whereas adolescents used more coping that involved persistence, alternate thinking and talking things over (taking personal responsibility). CONCLUSIONS: Youth with diabetes did not report stressors related to diabetes and its management as major themes in their daily lives. Clinical interventions based on perceptions of how youth understand and cope with stress are explored.


Subject(s)
Adaptation, Psychological , Diabetes Mellitus, Type 1/psychology , Stress, Psychological/etiology , Adolescent , Attitude to Health , Child , Chronic Disease , Female , Humans , Male , Stress, Psychological/epidemiology
4.
An Pediatr (Barc) ; 69(4): 355-7, 2008 Oct.
Article in Spanish | MEDLINE | ID: mdl-18928704

ABSTRACT

Multicystic dysplasia is the most common type of renal cystic disease, and it is one of the most common causes of an abdominal mass in infants. The contralateral system is also frequently abnormal. The most commonly associated anomalies are contralateral ureteropelvic junction obstruction and contralateral vesicoureteral reflux. In a few cases, multicystic dysplasia involves a horseshoe kidney or one pole of a duplex kidney. We present a female patient diagnosed with this condition at 9 years old, when she was being studied due to recurrent abdominal pain. The renal function was normal.


Subject(s)
Kidney/abnormalities , Multicystic Dysplastic Kidney/complications , Child , Female , Humans , Multicystic Dysplastic Kidney/diagnosis
5.
An. pediatr. (2003, Ed. impr.) ; 69(4): 355-357, oct. 2008. ilus
Article in Es | IBECS | ID: ibc-67688

ABSTRACT

La displasia renal multiquística es la variedad más frecuente de enfermedad quística renal y una de las causas más comunes de masa abdominal en recién nacidos y lactantes. Las anomalías contralaterales que se asocian con más frecuencia son la estenosis de la unión pieloureteral y el reflujo vesicoureteral. En muy pocos casos, la displasia renal multiquística está presente en uno de los segmentos de un riñón "en herradura" o en uno de los polos, en el caso de un doble sistema. Presentamos el caso de una paciente portadora de esta asociación de malformaciones diagnosticada a los 9 años de edad al ser estudiada por tener dolor abdominal recurrente. La función renal fue normal (AU)


Multicystic dysplasia is the most common type of renal cystic disease, and it is one of the most common causes of an abdominal mass in infants. The contralateral system is also frequently abnormal. The most commonly associated anomalies are contralateral ureteropelvic junction obstruction and contralateral vesicoureteral reflux. In a few cases, multicystic dysplasia involves a horseshoe kidney or one pole of a duplex kidney. We present a female patient diagnosed with this condition at 9 years old, when she was being studied due to recurrent abdominal pain. The renal function was normal (AU)


Subject(s)
Humans , Female , Child , Kidney/abnormalities , Kidney Diseases, Cystic/congenital , Kidney Neoplasms/complications , Kidney Neoplasms/therapy , Abdominal Pain/complications , Abdominal Pain/diagnosis , Furosemide/therapeutic use , Kidney/pathology , Pain/etiology , Osmolar Concentration , Kidney , Kidney Neoplasms , Tomography, Emission-Computed
6.
Rev Sci Instrum ; 78(5): 053703, 2007 May.
Article in English | MEDLINE | ID: mdl-17552821

ABSTRACT

An approach for automated nanotomography, a layer-by-layer imaging technique based on scanning probe microscopy (SPM), is presented. Stepwise etching and imaging is done in situ in a liquid cell of an SPM. The flow of etching and rinsing solutions after each etching step is controlled with solenoid valves which allow for an automated measuring protocol. The thermal drift and the drift of the piezo scanner is corrected by applying offsets calculated from the cross correlation coefficients between successive images. As an example, we have imaged human bone with approximately 10 nm resolution using tapping mode SPM and successive etching with hydrochloric acid.


Subject(s)
Image Enhancement/instrumentation , Microscopy, Scanning Probe/instrumentation , Nanostructures/ultrastructure , Nanotechnology/instrumentation , Robotics/instrumentation , Specimen Handling/instrumentation , Tomography, Optical/instrumentation , Image Enhancement/methods , Microscopy, Scanning Probe/methods , Nanotechnology/methods , Reproducibility of Results , Robotics/methods , Sensitivity and Specificity , Specimen Handling/methods , Tomography, Optical/methods
7.
Cell Mol Life Sci ; 63(13): 1494-500, 2006 Jul.
Article in English | MEDLINE | ID: mdl-16732426

ABSTRACT

Taste bud cells communicate with sensory afferent fibers and may also exchange information with adjacent cells. Indeed, communication between taste cells via conventional and/or novel synaptic interactions may occur prior to signal output to primary afferent fibers. This review discusses synaptic processing in taste buds and summarizes results showing that it is now possible to measure real-time release of synaptic transmitters during taste stimulation using cellular biosensors. There is strong evidence that serotonin and ATP play a role in cell-to-cell signaling and sensory output in the gustatory end organs.


Subject(s)
Cell Communication , Chemoreceptor Cells/physiology , Signal Transduction/physiology , Taste Buds/physiology , Adenosine Triphosphate/metabolism , Animals , Forecasting , Humans , Neurotransmitter Agents , Receptors, Serotonin/metabolism , Serotonin/metabolism
8.
Bol. pediatr ; 46(197): 244-250, 2006. ilus, tab
Article in Es | IBECS | ID: ibc-048903

ABSTRACT

El conducto (ductus) arterioso persistente (DAP) es una enfermedad frecuente en el prematuro. La indometacina intravenosa es el tratamiento estándar para su cierre, pero recientemente se ha empezado a utilizar el ibuprofeno intravenoso como alternativa o, incluso, como fármaco de primera elección, ya que algunas revisiones de evidencia Ahan mostrado igual eficacia, aunque menos oliguria y mayor porcentaje de enfermedad pulmonar crónica (EPC). Sin embargo, a pesar del cambio en la prescripción, también existe la apreciación clínica de mayor porcentaje de fracasos en los recién nacidos tratados con ibuprofeno. Este estudio pretende comparar ibuprofeno frente a indometacina en el cierre del DAP para evaluar su efectividad y seguridad. Material y métodos: se realizó un estudio retrospectivo transversal que abarcó el período comprendido desde el 01/01/2000 al 31/12/2004. Se evaluaron los casos diagnosticados de DAP en prematuros de bajo peso al nacer. Resultados: los resultados muestran que en el 62% de los casos donde se utilizó un cierre farmacológico se hizo con indometacina (en un período de 3 años) frente al 38% con ibuprofeno (en un período de 2 años). Los parámetros de eficacia muestran que el número de dosis necesaria para el cierre del DAP se duplica para el ibuprofeno, así como la necesidad de un nuevo ciclo de tratamiento. El porcentaje de reapertura de DAP fue de un 45,6% frente al 11,1% y el número de casos donde no se cerró el DAP también fue mayor para el ibuprofeno (9% frente al 0%). Otros parámetros como necesidad de cierre quirúrgico y porcentaje de fracaso a la semana de la primera dosis fueron similares para los dos fármacos. En cuanto a la seguridad los parámetros de EPC y mortalidad del recién nacido se muestran desfavorables para el ibuprofeno y en ninguno de los recién nacidos tratados se produjo oliguria. Conclusión: el ibuprofeno presenta algunos parámetros de eficacia desfavorables frente a indometacina, lo que incrementa su coste. En cuanto a la seguridad nuestros datos concuerdan con revisiones publicadas, aunque no se produjo oliguria con ninguno de los fármacos


Patent ductus arteriosus (PDA) is a frequent disease in the premature baby. Intravenous Indomethacin is the standard treatment used to close the duct but recently intravenous ibuprofen has been prescribed as an alternative or even a firstchoice drug because recent type Aevidence has shown it to be equally effective although with less oliguria and a large percentage of chronic pulmonary disease( CPD). However, with this change of prescription a higher percentage of failures in new-born children treated with Ibuprofen has been perceived. This study attempts to compare Ibuprofen with Indomethacin and to assess their safety and effectiveness in treating PDA. Material and methods: a cross-sectional retrospective study was carried out that included the period 01/01/2000 to 31/12/2004. The cases of PDA diagnosed in premature babies with low birth weight were evaluated. Results: the results show that in those cases where the duct was closed by pharmacological means 62% were treated with indomethacin (over a three year period) and 38% with ibuprofen (over a two year period). The parameters of effectiveness show that the number of doses needed to close the duct is double for Ibuprofen and a new cycle of treatment is required. The percentage of cases where the duct reopened was 45% with ibuprofen as opposed to 11% with indomethacin and the number of cases where the PDA failed to close was also greater with Ibuprofen (9% compared to 0%). Other parameters such as the need to close the PDA surgically and the percentage of failures a week after the first close were similar for both drugs. As regards safety the parameters of CPD and the mortality of the new-born babies were unfavourable for Ibuprofen although there was no evidence of oliguria in any of the children treated. Conclusions: ibuprofen, unlike Indomethacin, displays certain unfavourable parameters regarding its effectiveness and is also more costly. As far as safety is concerned our data agree with other published studies although oliguria did not take place with either of the drugs


Subject(s)
Male , Female , Infant, Newborn , Humans , Ductus Arteriosus, Patent/drug therapy , Cyclooxygenase Inhibitors/therapeutic use , Cardiovascular Agents/therapeutic use , Indomethacin/therapeutic use , Ibuprofen/therapeutic use , Treatment Outcome , Retrospective Studies , Cross-Sectional Studies
9.
Arch Ital Biol ; 143(2): 87-96, 2005 May.
Article in English | MEDLINE | ID: mdl-16106989

ABSTRACT

CHO cells transfected with high-affinity 5HT receptors were used to detect and identify the release of serotonin from taste buds. Taste cells release 5HT when depolarized or when stimulated with bitter, sweet, or sour tastants. Sour- and depolarization-evoked release of 5HT from taste buds is triggered by Ca2+ influx from the extracellular fluid. In contrast, bitter- and sweet-evoked release of 5HT is triggered by Ca2+ derived from intracellular stores.


Subject(s)
Biosensing Techniques/methods , Serotonin/metabolism , Signal Transduction/physiology , Synaptic Transmission/physiology , Taste Buds/metabolism , Taste/physiology , Adenosine Triphosphate/metabolism , Adenosine Triphosphate/pharmacology , Animals , CHO Cells , Calcium Signaling/drug effects , Calcium Signaling/physiology , Cell Communication/drug effects , Cell Communication/physiology , Cricetinae , Epithelial Cells/metabolism , Female , Fura-2 , Indicators and Reagents , Mice , Organ Culture Techniques , Receptors, Serotonin/drug effects , Receptors, Serotonin/metabolism , Serotonin/pharmacology , Signal Transduction/drug effects , Synaptic Transmission/drug effects , Taste Buds/drug effects
10.
Neurology ; 63(6): 1124-6, 2004 Sep 28.
Article in English | MEDLINE | ID: mdl-15452317

ABSTRACT

A retrospective review of the safety, tolerability, and efficacy of vagus nerve stimulation (VNS) in 48 patients with intractable partial epilepsy was performed. Side effects were few and mild to moderate. Mean seizure frequency decreased by 26% after 1 year, 30% after 5 years, and 52% after 12 years with VNS treatment.


Subject(s)
Electric Stimulation Therapy , Epilepsies, Partial/therapy , Vagus Nerve/physiopathology , Adolescent , Adult , Child , Child, Preschool , Electric Stimulation Therapy/adverse effects , Electric Stimulation Therapy/instrumentation , Electrodes, Implanted , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Patient Acceptance of Health Care , Patient Dropouts , Retrospective Studies , Treatment Outcome
11.
Chem Senses ; 29(6): 473-82, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15269119

ABSTRACT

Monosodium glutamate (MSG) has a multifaceted, unusual taste to humans. Rats and other rodents also detect a complex taste to MSG. Responses of the chorda tympani nerve (CT) to glutamate applied to the front of the tongue were recorded in 13 anesthetized rats. Whole-nerve responses to 30 mM, 100 mM and 300 mM MSG mixed with 300 mM sucrose were recorded before and after adding 30 micro M amiloride to the rinse and stimulus solutions. Responses of CT single fibers were also recorded. Predictions from models of whole-nerve responses to binary mixtures were compared to the observed data. Results indicated that MSG-elicited CT responses have multiple sources, even in an amiloride-inhibited environment in rats. Those sources include responses of sucrose-sensitive CT neural units, which may provide the substrate for a sucrose-glutamate perceptual similarity, and responses of sucrose-insensitive CT neural units, which may respond synergistically to MSG-sucrose mixtures.


Subject(s)
Chorda Tympani Nerve/physiology , Food Additives/pharmacology , Sodium Glutamate/pharmacology , Sucrose/pharmacology , Sweetening Agents/pharmacology , Taste , Amiloride/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Synergism , Electrophysiology , Food Additives/administration & dosage , Male , Nerve Fibers/drug effects , Nerve Fibers/physiology , Rats , Rats, Sprague-Dawley , Sodium Glutamate/administration & dosage , Sucrose/administration & dosage , Sweetening Agents/administration & dosage , Taste Buds/drug effects , Taste Buds/physiology
12.
Chem Senses ; 29(4): 291-9, 2004 May.
Article in English | MEDLINE | ID: mdl-15150142

ABSTRACT

Taste aversion studies have demonstrated that rats conditioned to avoid monosodium glutamate (MSG) with amiloride added to reduce the intensity of the sodium component of MSG taste, generalize this aversion to aspartic acid and to L-AP4, but not to ionotropic glutamate receptor agonists. That is, MSG, L-AP4 and aspartate have similar tastes to rats. However, conditioned taste aversion methods are unable to show to what extent the tastes of two substances are different. If two substances activate the same afferent processes (e.g. taste receptors), they are likely to produce the same tastes, but if they activate different afferent processes, the subject may detect differences between the tastes of the substances. In this study, rats were tested to determine if they could discriminate between the tastes of these agonists and MSG. We also established the detection thresholds for NMDA, aspartic acid and L-AP4, with and without amiloride (a sodium channel antagonist). Taste threshold values were 1-4 mM for NMDA and aspartic acid and 0.5-2.5 microM for L-AP4. None were affected by 30 micro M amiloride. Rats could readily distinguish between the tastes of MSG and NMDA but they had difficulty discriminating between the tastes of aspartic acid and MSG. Rats could also easily distinguish between 10-100 mM MSG and 0.01-5 mM L-AP4. However, in two separate experiments error rates increased significantly when L-AP4 concentrations were between 10-100 mM, indicating that the tastes of L-AP4 and MSG were similar at these concentrations.


Subject(s)
Discrimination, Psychological/physiology , Excitatory Amino Acid Agonists/pharmacology , Sodium Glutamate/pharmacology , Taste/physiology , Amiloride/pharmacology , Aminobutyrates/pharmacology , Animals , Aspartic Acid/pharmacology , Avoidance Learning , Male , N-Methylaspartate/pharmacology , Rats , Taste Threshold
13.
Org Lett ; 5(16): 2773-6, 2003 Aug 07.
Article in English | MEDLINE | ID: mdl-12889871

ABSTRACT

[reaction: see text] Intramolecular 1,3-dipolar cycloadditions of cinchona azides to the C10-C11 alkyne and C10-C11 olefin unit of the alkaloid have been designed via tandem strategy. A variety of fused triazoles and triazolines with a bis-azahomotwistane skeleton have been prepared. In trifluoroethanol, O-mesylcinchonidine 7-OMs and NaN(3) furnish triazole 8 as well as cage-expanded 1,5-diazatricyclo[4.4.1.0(3,8)]undecane derivative 10. Both fused triazoles 8 and 10 are formed with retention of configuration at C9 and C3, respectively. 1-Azabicyclo[3.2.2]cage expansion is shown to be reversible.

14.
J Physiol ; 547(Pt 2): 475-83, 2003 Mar 01.
Article in English | MEDLINE | ID: mdl-12562903

ABSTRACT

Sour taste is elicited by acids. How taste cells transduce sour taste is controversial because acids (specifically protons) have diverse effects on cell membranes. Consequently, it is difficult to differentiate between events related to sour taste transduction per se and unrelated effects of protons. We have studied acid taste transduction in mouse taste buds using a lingual slice preparation where it is possible to measure changes in pH and [Ca2+]i simultaneously in taste cells. Focal application of citric acid or HCl to the apical tips of taste buds produced widespread acidification of the entire taste bud. Citric acid was effective at a pH of approximately 4, but HCl only at a pH of approximately 1.5. Despite acidification of the whole taste bud, only a select few taste cells exhibited Ca2+ responses. Acid-evoked Ca2+ responses were dose dependent in a range consistent with them being sour-taste responses. Cells exhibiting acid-evoked Ca2+ responses also responded to KCl depolarization. Acid-evoked Ca2+ responses were blocked by Ba2+ (2 mM) and Cd2+ (500 microM), suggesting that acid responses are generated by Ca2+ influx through depolarization-gated Ca2+ channels. Removing extracellular Ca2+ reduced acid-evoked Ca2+ responses, but depleting intracellular Ca2+ stores with thapsigargin had no effect, suggesting that acid taste responses are generated by an influx of extracellular Ca2+. Neither Cs+ (500 microM) nor amiloride (100 microM) affected acid-evoked Ca2+ responses, suggesting that neither hyperpolarization-activated cyclic nucleotide-gated cation (pacemaker) channels nor epithelial Na+ channels, respectively, transduce sour taste. Collectively, the results indicate that acids, especially weak acids, acidify the taste bud and evoke depolarization-induced Ca2+ entry into a select subset of taste cells. The primary transducer protein(s) for sour taste remain undiscovered.


Subject(s)
Calcium/metabolism , Citric Acid/pharmacology , Hydrochloric Acid/pharmacology , Protons , Taste Buds/metabolism , Taste/physiology , Animals , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Hydrogen-Ion Concentration , In Vitro Techniques , Mice , Mice, Inbred DBA , Microscopy, Confocal , Taste Buds/cytology , Taste Buds/drug effects , Tongue/cytology , Tongue/drug effects , Tongue/metabolism
15.
Chem Senses ; 27(4): 375-82, 2002 May.
Article in English | MEDLINE | ID: mdl-12006377

ABSTRACT

Conditioned taste aversion studies have demonstrated that rats conditioned to avoid monosodium glutamate (MSG) with amiloride added to reduce the intensity of the sodium component of MSG taste, will generalize an aversion for MSG to sucrose and vice versa. This suggests that taste transduction for sodium, sucrose and MSG may intersect at some point. Generalization of conditioned taste aversion indicates that two substances share similar taste features, but it does not reveal the extent of their differences. In this study, we tested how well rats can discriminate sucrose and MSG under a variety of conditions. Water-deprived rats were trained on a combination of water reinforcement and shock avoidance to discriminate between MSG and sucrose, both with and without amiloride, and with and without equimolar NaCl in all solutions. In the absence of amiloride, rats reliably distinguished between MSG and sucrose down to 10 mM solutions. However, they could correctly identify solutions only above 50 mM in the presence of amiloride, equimolar sodium chloride, or both. These results suggest that gustatory stimulation by MSG and sucrose interact somewhere in taste transduction, perhaps within taste receptor cells or gustatory afferent pathways.


Subject(s)
Discrimination, Psychological/drug effects , Sodium Glutamate/pharmacology , Sucrose/pharmacology , Taste/drug effects , Amiloride/pharmacology , Animals , Discrimination Learning/drug effects , Diuretics/pharmacology , Electroshock , Male , Rats , Rats, Sprague-Dawley , Taste Threshold/drug effects
16.
Arch Clin Neuropsychol ; 17(6): 583-93, 2002 Aug.
Article in English | MEDLINE | ID: mdl-14591857

ABSTRACT

MMPI-2 profiles of 93 presurgical intractable epilepsy patients were examined using Ward's method of cluster analysis. Three clusters were identified. The means of each cluster suggest that 45% of the sample had minimal psychological complaints, 30% presented with generalized clinical elevations, and 25% of the patients had profiles of intermediate elevations with a tendency to emphasize somatic complaints and/or depression. Gender, age of seizure onset, and seizure laterality were not found to be uniquely associated with the cluster profiles. Further examination of correlates of group membership is warranted to provide information for treatment planning.

17.
Eur J Neurosci ; 14(2): 203-9, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11553273

ABSTRACT

A wealth of indirect data suggest that the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate (S1P) receptor plays important roles in development. In vitro, it activates several forms of development-related signal transduction and regulates cellular proliferation, differentiation and survival. It is expressed during embryogenesis, and mutation of an H218-like gene in zebrafish leads to profound defects in embryonic development. Nevertheless, the in vivo functions served by H218 signalling have not been directly investigated. We report here that mice in which the H218 gene has been disrupted are unexpectedly born with no apparent anatomical or physiological defects. In addition, no abnormalities were observed in general neurological development, peripheral axon growth or brain structure. However, between 3 and 7 weeks of age, H218(-/-) mice have seizures which are spontaneous, sporadic and occasionally lethal. Electroencephalographic abnormalities were identified both during and between the seizures. At a cellular level, whole-cell patch-clamp recordings revealed that the loss of H218 leads to a large increase in the excitability of neocortical pyramidal neurons. Therefore, H218 plays an essential, unanticipated and functionally important role in the proper development and/or mediation of neuronal excitability.


Subject(s)
Cerebral Cortex/growth & development , Epilepsy/congenital , Pyramidal Cells/metabolism , Receptors, Cell Surface/deficiency , Receptors, G-Protein-Coupled , Signal Transduction/genetics , Action Potentials/drug effects , Action Potentials/genetics , Animals , Axons/metabolism , Axons/pathology , Bicuculline/pharmacology , Cerebral Cortex/pathology , Cerebral Cortex/physiopathology , Electroencephalography/drug effects , Epilepsy/genetics , Epilepsy/physiopathology , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Female , GABA Antagonists/pharmacology , Hippocampus/growth & development , Hippocampus/pathology , Hippocampus/physiopathology , Male , Mice , Mice, Knockout/genetics , Mice, Knockout/growth & development , Mice, Knockout/metabolism , Mice, Neurologic Mutants/genetics , Mice, Neurologic Mutants/growth & development , Mice, Neurologic Mutants/metabolism , Nervous System Malformations/genetics , Nervous System Malformations/metabolism , Nervous System Malformations/pathology , Neurologic Examination , Peripheral Nervous System/embryology , Peripheral Nervous System/metabolism , Peripheral Nervous System/pathology , Pyramidal Cells/drug effects , Pyramidal Cells/pathology , RNA, Messenger/metabolism , Receptors, Cell Surface/genetics , Receptors, Lysophospholipid , Seizures/congenital , Seizures/genetics , Seizures/physiopathology , Signal Transduction/drug effects
18.
Ann Neurol ; 50(2): 188-94, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11506401

ABSTRACT

Brain-derived neurotrophic factor (BDNF) has trophic effects and modulates synaptic transmission in the hippocampal formation in animal studies. It is also upregulated in acute and chronic epilepsy models and in human temporal lobe epilepsy. This study was undertaken to examine the effects of BDNF on fast synaptic transmission in the human epileptic dentate gyrus. Hippocampal specimens were acquired from patients with temporal lobe epilepsy during surgical removal of the anterior temporal lobe intended to treat the epileptic condition. Whole-cell patch-clamp recordings were obtained from dentate granule cells in transverse hippocampal slices in vitro. Application of BDNF increased the amplitude and frequency of spontaneous excitatory postsynaptic currents and increased the amplitude of evoked excitatory postsynaptic currents. BDNF had no effect on spontaneous inhibitory postsynaptic currents but produced a decrease in amplitude of evoked inhibitory postsynaptic currents. BDNF's effects were abolished by coapplication of the tyrosine kinase inhibitor K252a. Therefore, BDNF enhances fast excitatory transmission in the epileptic human dentate gyrus and may play an important role in epileptogenesis in temporal lobe epilepsy. This raises the possibility of designing therapies for this disorder that may be both anticonvulsant and antiepileptogenic.


Subject(s)
Brain-Derived Neurotrophic Factor/pharmacology , Dentate Gyrus/pathology , Dentate Gyrus/physiopathology , Epilepsy/pathology , Epilepsy/physiopathology , Synaptic Transmission/drug effects , Adolescent , Adult , Female , Humans , Male , Middle Aged , Synaptic Transmission/physiology , Time Factors
19.
Neuroreport ; 12(8): 1715-8, 2001 Jun 13.
Article in English | MEDLINE | ID: mdl-11409745

ABSTRACT

Non-NMDA type glutamate receptors are present in rat taste buds. However, the function of those receptors is not yet known. Developmental changes in the glutamate receptors in taste cells may provide clues to their functional role. We used a cobalt staining technique to determine at which stage in development functional non-NMDA glutamate receptors first appeared. Cobalt-stained taste bud cells first appeared in 20-day-old rats. The number of cobalt-stained cells increased with age and reached a maximum at 45 days. The shape of stained cells looked similar at all age groups. Cobalt-labeled cells appeared to be correlated with synaptic, not taste, glutamate receptors.


Subject(s)
Aging/metabolism , Animals, Newborn/metabolism , Cobalt/pharmacokinetics , Glutamic Acid/pharmacology , Receptors, Glutamate/metabolism , Taste Buds/metabolism , Animals , Animals, Newborn/growth & development , In Vitro Techniques , Rats , Rats, Sprague-Dawley , Receptors, N-Methyl-D-Aspartate/metabolism , Staining and Labeling
20.
Clin Neurophysiol ; 112(5): 836-44, 2001 May.
Article in English | MEDLINE | ID: mdl-11336899

ABSTRACT

OBJECTIVES: Definitive localization of an epileptic focus correlates with a favorable outcome following epilepsy surgery. This study was undertaken to determine the incremental value of data yielded for surgical decision making when using subdural electrodes alone and in addition to depth electrodes for temporal lobe epilepsy. METHODS: Standardized placement for intracranial electrodes included: (1) longitudinal placement of bilateral temporal lobe depth electrodes; (2) bilateral subtemporal subdural strips; and (3) bilateral orbitofrontal subdural strips. Sixty-three events were randomly reviewed for: (1) subdural electrodes alone; and (2) depth electrodes in conjunction with subdural electrodes. RESULTS: Of the 63 seizures, 54 (85.7%) demonstrated congruent lateralization to ipsilateral subtemporal subdural strip electrodes (based on depth electrode localization) when subdural strip electrodes were utilized alone. In 3 of 22 patients, 7 seizures demonstrated 'false localization' on subdural electrode analysis alone when compared with depth recording and post-surgical outcome. For these 3 patients, retrospective review of neuroimaging demonstrated suboptimal ipsilateral placement of subtemporal subdural electrodes with the most mesial electrode lateral to the collateral sulcus. Four additional patients had suboptimal placement of subtemporal subdural electrodes. Two of these 4 patients had congruent localization with subdural electrodes to ipsilateral depth electrodes despite suboptimal placement. Subtemporal subdural electrodes accurately localized for all seizures from the mesial temporal lobe when the mesial electrodes of the subtemporal subdural strip recorded mesial to the collateral sulcus from the parahippocampal region. CONCLUSION: We conclude that although there are high concordance rates between subdural and depth electrodes, localization of seizure onset based on subdural strip electrodes alone may result in inaccurate focus identification with potential for possible suboptimal treatment of temporal lobe epilepsy. When subtemporal subdural electrodes provide recording from the parahippocampal region, there is accurate localization of the seizure focus. If suboptimal placement occurs lateral to the collateral sulcus, the electroencephalographer cannot make a definitive identification of the seizure focus.


Subject(s)
Brain Mapping/methods , Electroencephalography/methods , Epilepsy, Temporal Lobe/physiopathology , Functional Laterality/physiology , Hippocampus/physiopathology , Temporal Lobe/physiopathology , Cognition , Electrodes , Electroencephalography/instrumentation , Epilepsy, Temporal Lobe/surgery , Hippocampus/pathology , Humans , Magnetic Resonance Imaging , Reproducibility of Results , Temporal Lobe/pathology , Temporal Lobe/surgery , Video Recording
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