Ultrasound-guided caudal blockade and sedation for paediatric surgery: a retrospective cohort study.

Data on safety and success rates of ultrasound-guided caudal blockade, performed on sedated children with an uninstrumented airway, are scarce. We performed a retrospective observational study of validated data from April 2014 to December 2020 in a paediatric cohort where the initial plan for anaesthetic management was sedation and caudal epidural without general anaesthesia or airway instrumentation. We examined success rates of this approach and rates of block failure and block-related complications. In total, 2547 patients ≤ 15 years of chronological age met inclusion criteria. Among the 2547 cases, including 453 (17.8%) former preterm patients, caudal-plus-sedation success rate was 95.1%. The primary anaesthesia plan was abandoned for general anaesthesia in 124 cases. Pain-related block failure in 83 (3.2%) was the most common cause for conversion. Complications included 39 respiratory events and 9 accidental spinal anaesthetics. Higher odds of pain-related block failure were associated with higher body weight (adjusted OR 1.063, 95%CI 1.035-1.092, p < 0.001) as well as with mid-abdominal surgery (e.g. umbilical hernia repair) (adjusted OR 15.11, 95%CI 7.69-29.7, p < 0.001), whereas extreme (< 28 weeks) former prematurity, regardless of chronological age, was associated with higher odds (adjusted OR 3.62, 95%CI 1.38-9.5, p = 0.009) for respiratory problems. Ultrasound-guided caudal epidural, performed under sedation with an uninstrumented airway, is an effective technique in the daily clinical routine. Higher body weight and mid-abdominal surgical procedures are risk factors for pain-related block failure. Patients who, regardless of chronological age, had been born as extreme preterm babies are at the highest risk for respiratory events.

Association between night-time surgery and occurrence of intraoperative adverse events and postoperative pulmonary complications.

BACKGROUND: The aim of this post hoc analysis of a large cohort study was to evaluate the association between night-time surgery and the occurrence of intraoperative adverse events (AEs) and postoperative pulmonary complications (PPCs). METHODS: LAS VEGAS (Local Assessment of Ventilatory Management During General Anesthesia for Surgery) was a prospective international 1-week study that enrolled adult patients undergoing surgical procedures with general anaesthesia and mechanical ventilation in 146 hospitals across 29 countries. Surgeries were defined as occurring during 'daytime' when induction of anaesthesia was between 8:00 AM and 7:59 PM, and as 'night-time' when induction was between 8:00 PM and 7:59 AM. RESULTS: Of 9861 included patients, 555 (5.6%) underwent surgery during night-time. The proportion of patients who developed intraoperative AEs was higher during night-time surgery in unmatched (43.6% vs 34.1%; P<0.001) and propensity-matched analyses (43.7% vs 36.8%; P=0.029). PPCs also occurred more often in patients who underwent night-time surgery (14% vs 10%; P=0.004) in an unmatched cohort analysis, although not in a propensity-matched analysis (13.8% vs 11.8%; P=0.39). In a multivariable regression model, including patient characteristics and types of surgery and anaesthesia, night-time surgery was independently associated with a higher incidence of intraoperative AEs (odds ratio: 1.44; 95% confidence interval: 1.09-1.90; P=0.01), but not with a higher incidence of PPCs (odds ratio: 1.32; 95% confidence interval: 0.89-1.90; P=0.15). CONCLUSIONS: Intraoperative adverse events and postoperative pulmonary complications occurred more often in patients undergoing night-time surgery. Imbalances in patients' clinical characteristics, types of surgery, and intraoperative management at night-time partially explained the higher incidence of postoperative pulmonary complications, but not the higher incidence of adverse events. CLINICAL TRIAL REGISTRATION: NCT01601223.

Intraoperative ventilation settings and their associations with postoperative pulmonary complications in obese patients.

BACKGROUND: There is limited information concerning the current practice of intraoperative mechanical ventilation in obese patients, and the optimal ventilator settings for these patients are debated. We investigated intraoperative ventilation parameters and their associations with the development of postoperative pulmonary complications (PPCs) in obese patients. METHODS: We performed a secondary analysis of the international multicentre Local ASsessment of VEntilatory management during General Anesthesia for Surgery' (LAS VEGAS) study, restricted to obese patients, with a predefined composite outcome of PPCs as primary end-point. RESULTS: We analysed 2012 obese patients from 135 hospitals across 29 countries in Europe, North America, North Africa, and the Middle East. Tidal volume was 8.8 [25th-75th percentiles: 7.8-9.9] ml kg-1 predicted body weight, PEEP was 4 [1-5] cm H2O, and recruitment manoeuvres were performed in 7.7% of patients. PPCs occurred in 11.7% of patients and were independently associated with age (P<0.001), body mass index ≥40 kg m-2 (P=0.033), obstructive sleep apnoea (P=0.002), duration of anaesthesia (P<0.001), peak airway pressure (P<0.001), use of rescue recruitment manoeuvres (P<0.05) and routine recruitment manoeuvres performed by bag squeezing (P=0.021). PPCs were associated with an increased length of hospital stay (P<0.001). CONCLUSIONS: Obese patients are frequently ventilated with high tidal volume and low PEEP, and seldom receive recruitment manoeuvres. PPCs increase hospital stay, and are associated with preoperative conditions, duration of anaesthesia and intraoperative ventilation settings. Randomised trials are warranted to clarify the role of different ventilatory parameters in obese patients. CLINICAL TRIAL REGISTRATION: NCT01601223.

Patient's and health care provider's perspectives on music therapy in palliative care - an integrative review.

BACKGROUND: The use of music as therapy in multidisciplinary end-of-life care dates back to the 1970s and nowadays music therapy (MT) is one of the most frequently used complementary therapy in in-patient palliative care in the US. However existing research investigated music therapy's potential impact mainly from one perspective, referring to either a quantitative or qualitative paradigm. The aim of this review is to provide an overview of the users' and providers' perspectives on music therapy in palliative care within one research article. METHODS: A systematic literature search was conducted using several databases supplemented with a hand-search of journals between November 1978 and December 2016. Inclusion criteria were: Music therapy with adults in palliative care conducted by a certified music therapist. Both quantitative and qualitative studies in English, German or a Scandinavian language published in peer reviewed journals were included. We aimed to identify and discuss the perspectives of both patients and health care providers on music therapy's impact in palliative care to forward a comprehensive understanding of it's effectiveness, benefits and limitations. We investigated themes mentioned by patients within qualitative studies, as well as commonly chosen outcome measures in quantitative research. A qualitative approach utilizing inductive content analysis was carried out to analyze and categorize the data. RESULTS: Twelve articles, reporting on nine quantitative and three qualitative research studies were included. Seven out of the nine quantitative studies investigated pain as an outcome. All of the included quantitative studies reported positive effects of the music therapy. Patients themselves associated MT with the expression of positive as well as challenging emotions and increased well-being. An overarching theme in both types of research is a psycho-physiological change through music therapy. CONCLUSIONS: Both quantitative as well as qualitative research showed positive changes in psycho-physiological well-being. The integration of the users´ and providers´ perspectives within future research applicable for example in mixed-methods designs is recommended.

An observational study of the macro- and micro-haemodynamic implications of epidural anaesthesia in children.

The haemodynamic implications of epidural anaesthesia in children are poorly documented. We report macro- and micro-haemodynamic data from an observational study of 25 children ranging from neonates to six-years old, who underwent surgery conducted with a specific combination of monitoring systems. We analysed 90 min of study-related monitoring after epidural catheterisation, with skin incision taking place after around 30 min. We recorded macrohaemodynamic parameters (monitored using LiDCOrapid) including heart rate, mean arterial pressure, cardiac output, stroke volume, systemic vascular resistance and stroke volume variation. Microhaemodynamic parameters (monitored using Invos™) included cerebral and peri-renal oxygenation. Based on the entire 90 min of study-related monitoring, we found significant increases in cardiac output (p = 0.009), stroke volume (p = 0.006) and stroke volume variation (p = 0.008), as well as decreases in systemic vascular resistance (p = 0.007) around 30 min after epidural blockade. There were no significant changes in heart rate, arterial pressure and cerebral or peri-renal oxygenation during these 90 min. Considering that the microhaemodynamic parameters were not affected by the macrohaemodynamic changes, we conclude that autoregulation of the brain and the kidneys was maintained in children under epidural anaesthesia.

Delaying surgery to perform CT scans for suspected appendicitis decreases the rate of negative appendectomies without increasing the rate of perforation nor postoperative complications.

PURPOSE: Negative appendectomies are costly and are embedded with unnecessary risks for the patients. A careful indication for surgery seems mandatory even more so, since conservative therapy emerges as a potential alternative to surgery. The aims of this population-based study were to analyze whether radiological examinations for suspected appendicitis decreased the rate of negative appendectomies without increasing the rate of perforation or worsening postoperative outcomes. METHOD: This study is a retrospective analysis of a prospective population-based database. The data collection included preoperative investigations and intraoperative and postoperative outcomes. RESULTS: Based on 2559 patients, the rate of negative appendectomies decreased significantly with the use of CT scan as compared to clinical evaluation only (9.3 vs 5 %, p = 0.019), whereas ultrasonography alone was not able to decrease this rate (9.3 vs 6.2 %, p = 0.074). Delaying surgery for radiological investigation did not increase the rate of perforation (18.1 vs 19.2 %; adjusted odds ratio (OR) 1.01; 0.8-1.3; p = 0.899). Postoperative complications (surgical reintervention, postoperative wound infection, postoperative hematoma, postoperative intra-abdominal abscess, postoperative ileus) were all comparable. CONCLUSION: In this population-based study, CT scan was the only radiological modality that significantly reduced the rate of negative appendectomy. The delay induced by such additional imaging did not increase perforation nor complication rates. Abdominal CT scans for suspected appendicitis should therefore be more frequently used if clinical findings are unconclusive.

Clinical ex vivo lung perfusion--pushing the limits.

Ex vivo lung perfusion (EVLP) provides the ability to evaluate donor lungs before transplantation. Yet, limited prospective clinical data exist with regard to its potential to recondition unacceptable donor lungs. This paper summarizes the results of a prospective study of lung transplantation using only initially unacceptable donor lungs, which were improved by EVLP for 2-4 h. From March 2010-June 2011, 13 lungs were evaluated ex vivo. Median donor PaO(2) at FiO(2) 1.0/PEEP5 was 216 mmHg (range 133-271). Four lungs, all with trauma history, showed no improvement and were discarded. Nine lungs improved to a ΔPO(2) higher than 350 mmHg. Median PvO(2) at final assessment in these lungs was 466 mmHg (range 434-525). These lungs were transplanted with a median total ischemic time of 577 min (range 486-678). None of the patients developed primary graft dysfunction grades 2 or 3 within 72 h after transplantation. One patient with secondary pulmonary hypertension was left on a planned prolonged extracorporeal membrane oxygenation postoperatively. Median intubation time was 2 days. Thirty-day mortality was 0%. During the observation period, 119 patients received standard lung transplantation with comparable perioperative outcome. EVLP has a significant potential to improve the quality of otherwise unacceptable donor lungs.

Randomized clinical trial comparing double-lumen tube and EZ-Blocker for single-lung ventilation.

BACKGROUND: In several clinical situations, lung separation and single-lung ventilation (SLV) is essential. In these cases, the double-lumen tube (DLT) is the most widely used device. Bronchial blocker such as Univent or Arndt Blocker serves as an alternative. The EZ-Blocker(®) (EZ; AnaesthetIQ B.V., Rotterdam, The Netherlands) is a new device promising to exceed clinical performance of DLT. The aim of this study was to assess the clinical performance of EZ in comparison with conventional left-sided DLT. METHODS: Forty adult patients undergoing elective thoracic surgery requiring thoracotomy and SLV were included in this study. The patients were randomly assigned to one of two groups: EZ (combined with conventional 7.5 or 8.5 mm single-lumen tube) or DLT (37 or 39 Fr left-sided DLT). Time for intubation procedure and time to verification of the correct position of EZ or DLT using fibreoptic bronchoscopy (FOB) were recorded. After surgery, a thoracic surgeon rated the quality of collapse of the lung (1-3 on a three-level scale). RESULTS: Time for intubation using DLT 85.5 (54.8) s was significantly faster (P<0.001) than using EZ 192 (89.7) s, whereas time for bronchoscopy was not significantly different (P=0.556). Conditions of surgery were rated equally [DLT 1.3 (0.6) vs EZ 1.4 (0.6), P=0.681]. CONCLUSIONS: Although time for intubation was longer with the EZ, the device proved to be an efficient and easy-to-use device. The EZ is a valuable alternative device to conventional DLT. Verification of the correct position of the EZ by FOB seems to be obligatory. This study was registered at http://www.clinicaltrials.gov (identifier: NCT01171560).

Hepatocyte differentiation in vitro: initiation of tyrosine aminotransferase expression in cultured fetal rat hepatocytes.

A fetal rat hepatocyte culture system has been used to study the molecular mechanisms of tyrosine aminotransferase (TAT) gene expression during development. It has previously been shown that TAT activity can be detected in 19-d, but not 15-d, gestation hepatocytes on the first day of culture (Yeoh, G. C. T., F. A. Bennett, and I. T. Oliver. 1979. Biochem. J. 180:153-160). In this study enzyme activity, synthesis, and mRNA levels were determined in hepatocytes isolated from 13-, 15-, and 19-d gestation rats maintained in culture for 1, 2, or 3 d and exposed to dexamethasone. TAT expression is barely detectable in 13-d gestation hepatocytes even after 3 d in culture. Hepatocytes isolated from 15-d gestation fetuses have undetectable levels of enzyme activity and synthesis on the first day of culture; both can be assayed by days 2 and 3. TAT mRNA levels in these hepatocytes, measured by hybridization with a specific cDNA, increase substantially during culture. TAT activity, synthesis, and mRNA are evident on the first and subsequent days of culture in 19-d gestation hepatocytes. Transcription measurements in isolated nuclei indicate that the increase in TAT mRNA in 15- and 19-d gestation hepatocytes is associated with an increase in transcription of the gene. Immunocytochemical studies demonstrated that the increase in TAT expression correlated with an increase in the proportion of hepatocytes expressing the enzyme, rather than a simultaneous increase in all hepatocytes. These results support the proposal that a subpopulation of 15-d fetal hepatocytes undergo differentiation in culture with respect to TAT.

Survival of frogs in low temperature.

Anurans that hibernate at or near the ground surface can survive prolonged exposure to low winter temperatures of northern latitudes by tolerance to freezing. An accumulation of glycerol during winter was correlated with frost tolerance, indicating that this compound is associated with natural tolerance to freezing in a vertebrate.

Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro.

BACKGROUND: Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32). OBJECTIVES: To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation. METHODS: The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32). CONCLUSIONS: Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.

Ultrafast dynamics and coherent oscillations in ethylene and ethylene-d4 excited at 162 nm.

The fifth harmonic (162 nm, 11 fs), generated in a short argon cell from 12 fs Ti-sapphire laser pulses, was used to excite C2H4 and C2D4 in the maximum of the first pi pi* transition. Around 10% of the molecules were excited to the pi3s Rydberg state instead. The subsequent motion of the wave packet, moving over the potentials from the Franck-Condon region down to the ground state, was monitored by nonresonant ionization at 810 nm with mass-selective detection of the ion yield. Five time constants (from approximately 20 fs in excited states to 0.6-11 ps in the hot ground state) and four coherent oscillations (CC stretch and torsion vibrations or hindered free rotation) were determined for each isotopomer. The initial relaxation follows a superposition of CC twist and stretch coordinates; this explains a surprisingly small deuterium isotope effect of the initial time constant (21 versus 24 fs). Also the vibrations in the Franck-Condon region have such a mixed character and a correspondingly small isotope shift. From the perpendicular minimum the wave packet reaches (within 17 or 21 fs for the two isotopomers) a conical intersection via a direction that also involves partial hydrogen migration. This is concluded from the detection of ethylidene (CH3CH), formed simultaneously with ground-state ethylene. This carbene isomerizes in the ground state within 0.6 ps (1.6 ps for CD3CD) to ethylene. Two time constants for dissociation (4.5 and 11 ps) in the hot ground state were also identified. The small yields of bimolecular reactions (photodimerization, addition reactions involving a "suddenly polarized" excited state, carbene reactions) are interpreted in terms of the short lifetimes. It is pointed out that the relaxation path starting from the Rydberg state merges into that from the pi pi* state; nevertheless, there is a wavelength dependence in the photochemistry of olefins, because due to a momentum effect the wave packet remembers from which state it came.

Nucleolar RNA synthesis in the liver of partially hepatectomized and cortisol-treated rats.

RNA synthesis by isolated nucleoli from rat liver is significantly enhanced 12--14 h after partial hepatectomy and 4 h after cortisol administration. The increased RNA synthetic capactiy is demonstrable also in the respective high salt nucleolar extracts and in Biogel A-1.5 filtration fractions of the nucleolar extracts. DNA saturation experiments using nucleoli and Biogel fractions from control and treated animals as RNA polymerase source, have demonstrated, that independent of the extent of RNA synthesis, saturation of transcription is reached at the same concentration of exogenous template. We conclude that the activity and not the amount of nucleolar RNA polymerase is increased as a result of partial hepatectomy or cortisol administration. Parallel to the effects on RNA polymerase, the activity, of RNA-degrading enzymes present in nucleoli is also enhanced by the same treatment.

Essential role of CREB family proteins during Xenopus embryogenesis.

The leucine zipper transcription factors cAMP response element binding protein (CREB), cAMP response element modulatory protein (CREM) and activating transcription factor 1 (ATF1) bind to the cAMP response element (CRE) with the palindromic consensus sequence TGACGTCA. Their transcriptional activities are dependent on serine phosphorylation induced by various extracellular signals such as hormones, growth factors and neurotransmitters. Here we show that CREB is the predominant CRE-binding protein in Xenopus embryos and that it plays an essential role during early development. The importance of CREB for morphogenetic processes was assessed by injection of RNA encoding a dominant-negative form of CREB that is fused to a truncated progesterone receptor ligand binding domain. In this fusion protein, a dominant-negative function can be induced by application of the synthetic steroid RU486 at given developmental stages. The inhibition of CREB at blastula and early gastrula stages leads to severe posterior defects of the embryos reflected by strong spina bifida, whereas the inhibition of CREB at the beginning of neurulation resulted in stunted embryos with microcephaly. In these embryos, initial induction of neural and mesodermal tissues is not dependent on CREB function, as genes such as Otx2, Krox20, Shh and MyoD are still expressed in injected embryos. But the expression domains of Otx2 and MyoD were found to be distorted reflecting the abnormal development in both neural and somitic derivatives. In summary, our data show that CREB is essential during several developmental stages of Xenopus embryogenesis.

Role of cyclic AMP in the control of cell-specific gene expression.

Genes have to be expressed in specific cell types at appropriate times of development dependent on external signals. cAMP signaling occurs in all cells, thus raising the question of how this signal transduction pattern is integrated into mechanisms determining cell-specific gene expression. We have analyzed expression of the tyrosine aminotransferase gene as a model to study the basis of this cell type specificity of hormone induction. We found that cell-type-specific expression is generated by combined action of cAMP signal-dependent and liver cell-specific transcription factors. The interdependence of the cAMP response element and an element determining liver cell specificity enables a gene to respond to an ubiquitous signal in a cell-specific manner.

Functionality or aesthetics? A pilot study of music therapy in the treatment of multiple sclerosis patients.

INTRODUCTION: Neuro-degenerative diseases are, and will remain, an enormous public health problem. Interventions that could delay disease onset even modestly will have a major public health impact. The aim of this study is to see which components of the illness are responsive to change when treated with music therapy in contrast to a group of patients receiving standard medical treatment alone. MATERIAL AND METHODS: Twenty multiple sclerosis patients (14 female, 6 male) were involved in the study, their ages ranging from 29 to 47 years. Ten participants formed the therapy group, and 10 the matched control group matched by age, gender and the standard neurological classification scheme Expanded Disability Status Scale (EDSS). Exclusion criteria were pregnancy and mental disorders requiring medication. Patients in the therapy group received three blocks of music therapy in single sessions over the course of the one-year project (8-10 sessions, respectively). Measurements were taken before therapy began (U1), and subsequently every three months (U2-U4) and within a 6-month follow-up without music therapy (U5) after the last consultation. Test battery included indicators of clinical depression and anxiety (Beck Depression Inventory and Hospital Anxiety and Depression Scale), a self-acceptance scale (SESA) and a life quality assessment (Hamburg Quality of Life Questionnaire in Multiple Sclerosis). In addition, data were collected on cognitive (MSFC) and functional (EDSS) parameters. RESULTS: There was no significant difference between the music-therapy treatment group and the control group. However, the effect size statistics comparing both groups show a medium effect size on the scales measuring self-esteem (d, 0.5423), depression HAD-D (d, 0.63) and anxiety HAD-A (d, 0.63). Significant improvements were found for the therapy group over time (U1-U4) in the scale values of self-esteem, depression and anxiety. In the follow-up, scale values for fatigue, anxiety and self-esteem worsen within the group treated with music therapy. DISCUSSION: A therapeutic concept for multiple sclerosis, which includes music therapy, brings an improvement in mood, fatigue and self-acceptance. When music therapy is removed, then scale scores worsen and this appears to intimate that music therapy has an influence.

Human platelets exclusively bind oxidized low density lipoprotein showing no specificity for acetylated low density lipoprotein.

The widely studied macrophage scavenger receptor system is known to bind both acetylated low density lipoprotein and oxidized low density lipoprotein. Although only the latter ligand has been shown to occur in vivo, acetylated low density lipoprotein is often used to evaluate the contribution of scavenger receptors to different (patho)physiologic processes, assuming that all existing subtypes of scavenger receptors recognise both lipoproteins. In the present work, we identify human platelets as the first natural cell type to bind oxidized low density lipoprotein without showing specificity for acetylated low density lipoprotein. Consequently, platelets possess exclusive receptor(s) for oxidized low density lipoprotein distinct from the 'classical' scavenger receptor AI/AII. From the data presented in this work, we conclude that the class B scavenger receptor CD36 (GPIV) is responsible for this exclusive oxidized low density lipoprotein binding.

Expression of activating transcription factor-2, serum response factor and cAMP/Ca response element binding protein in the adult rat brain following generalized seizures, nerve fibre lesion and ultraviolet irradiation.

The expression of the constitutive transcription factors activating transcription factor-2 (ATF-2), serum response factor (SRF) and cAMP/Ca response element binding factor (CREB), and the phosphorylation of SRF and CREB were studied in the untreated adult rat nervous system and following seizure activities and neurodegenerative stimuli. In the untreated rat, intense nuclear SRF immunoreactivity was present in the vast majority of neurons in the forebrain, cortex, striatum, amygdala and hippocampus, and in some scattered neurons in the medulla and spinal cord. In contrast, SRF immunoreactivity was absent in the midline areas of the forebrain, e.g., the globus pallidum and septum, and in the hypothalamus, thalamus, mesencephalon and motoneurons. Nuclear ATF-2 was expressed at high levels in apparently all neurons, but not glial cells, throughout the neuraxis except for those neuronal populations which exhibit a high basal level of c-Jun, i.e. dentate gyrus and the motoneurons of cranial and somatosensory neurons. CREB immunoreactivity was present at a rather uniform intensity in all neuronal and glial cells throughout the neuraxis. Two hours, but not 5 h or 24 h, following systemic application of kainic acid, an increase in SRF was detectable by western blot analysis in hippocampal and cortical homogenates whereas the expression of ATF-2 and CREB did not change. Phosphorylation of CREB at serine 133 and of SRF at serine 103 were studied with specific antisera. In untreated rats, intense phosphoCREB and phosphoSRF immunoreactivities labelled many glial cells and/or neurons with the highest levels in the dentate gyrus, the entorhinal cortex and the retrosplenial cortex. Following kainate-induced seizures, phosphoSRF-IR but not phosphoCREB-IR transiently increased between 0.5 h and 2 h. Following transection of peripheral or central nerve fibres such as optic nerve, medial forebrain bundle, vagal and facial nerve fibres, ATF-2 rapidly decreased in the axotomized neurons during that period when c-Jun was rapidly expressed. SRF remained unchanged and CREB disappeared in some axotomized subpopulations. Similar to axotomy, c-Jun increased and ATF-2 decreased in cultured adult dorsal root ganglion neurons following ultraviolet irradiation. The distribution of SRF and ATF-2 suggests that their putative target genes c-fos, junB, krox-24 and c-jun can be independently regulated from SRF and ATF-2. The suppression of ATF-2 and the expression of c-Jun following axotomy and ultraviolet irradiation might be part of a novel neuronal stress response in the brain that strongly resembles the stress response characterized in non-neuronal cells.

Hallux duplication, postaxial polydactyly, absence of the corpus callosum, severe mental retardation, and additional anomalies in two unrelated patients: a new syndrome.

Two unrelated patients, a 4-year-old boy and a 2 1/2-year-old girl, presented with a similar pattern of abnormalities. Both had severe mental retardation, macrocephaly, absence of the corpus callosum, unusual facial appearance, duplication of hallucal phalanges, postaxial hexadactyly of finger phalanges, and 2/3-syndactyly of toes. The boy also had postaxial hexadactyly of toe phalanges, inguinal hernias and umbilical hernia, and growth retardation. We suspect a common cause of this apparently "new" syndrome, most likely a gene mutation.

Psychiatric symptoms and CAG expansion in Huntington's disease.

The mutation responsible for Huntington's disease (HD) is an elongated CAG repeat in the coding region of the IT15 gene. A PCR-based test with high sensitivity and accuracy is now available to identify asymptomatic gene carriers and patients. An inverse correlation between CAG copy number and age at disease onset has been found in a large number of affected individuals. The influence of the CAG repeat expansion on other phenotypic manifestations, especially specific psychiatric symptoms has not been studied intensively. In order to elucidate this situation we investigated the relation between CAG copy number and distinct psychiatric phenotypes found in 79 HD-patients. None of the four differentiated categories (personality change, psychosis, depression, and nonspecific alterations) showed significant differences in respect to size of the CAG expansion. In addition, no influence of individual sex on psychiatric presentation could be found. On the other hand in patients with personality changes maternal transmission was significantly more frequent compared with all other groups. Therefore we suggest that clinical severity of psychiatric features in HD is not directly dependent on the size of the dynamic mutation involved. The complex pathogenetic mechanisms leading to psychiatric alterations are still unknown and thus genotyping does not provide information about expected psychiatric symptoms in HD gene carriers.