High-functioning autism patients share similar but more severe impairments in verbal theory of mind than schizophrenia patients.

BACKGROUND: Evidence suggests that autism and schizophrenia share similarities in genetic, neuropsychological and behavioural aspects. Although both disorders are associated with theory of mind (ToM) impairments, a few studies have directly compared ToM between autism patients and schizophrenia patients. This study aimed to investigate to what extent high-functioning autism patients and schizophrenia patients share and differ in ToM performance. METHODS: Thirty high-functioning autism patients, 30 schizophrenia patients and 30 healthy individuals were recruited. Participants were matched in age, gender and estimated intelligence quotient. The verbal-based Faux Pas Task and the visual-based Yoni Task were utilised to examine first- and higher-order, affective and cognitive ToM. The task/item difficulty of two paradigms was examined using mixed model analyses of variance (ANOVAs). Multiple ANOVAs and mixed model ANOVAs were used to examine group differences in ToM. RESULTS: The Faux Pas Task was more difficult than the Yoni Task. High-functioning autism patients showed more severely impaired verbal-based ToM in the Faux Pas Task, but shared similar visual-based ToM impairments in the Yoni Task with schizophrenia patients. CONCLUSIONS: The findings that individuals with high-functioning autism shared similar but more severe impairments in verbal ToM than individuals with schizophrenia support the autism-schizophrenia continuum. The finding that verbal-based but not visual-based ToM was more impaired in high-functioning autism patients than schizophrenia patients could be attributable to the varied task/item difficulty between the two paradigms.

Neurotrauma research in Taiwan.

Because of the rapid industrial and economic growth, Taiwan and other developing countries have faced an enormous increase in the number of motorcycles, which has subsequently caused a rapid increase of the motorcycle-related traumatic brain injuries (TBI). In order to tackle this serious problem, stepwise approaches for TBI were implemented in Taiwan from 1991 to 2007. Step 1 was to do a nationwide TBI registry in order to identify the risk factors and determinants. We found that the major cause of TBI in Taiwan was motorcycle-related injury, and very few motorcyclists wore a helmet. Step 2 was to launch the implementation of the helmet use law on June 1, 1997. A rapid decline of TBI hospitalizations and deaths was demonstrated soon thereafter. Step 3 was to enroll into international collaborations with the Global Spine and Head Injury Prevention Project (Global SHIP Project) groups for TBI. The comparative results thus obtained could be used to develop prevention strategies for developing countries. Step 4 was to implement clinical researches for TBI, which included a Propofol study, hyperbaric oxygen therapy (HBOT), brain parenchymal oxygen (PbtO2) monitoring, etc. Step 5 was to develop guidelines for the management of severe TBI in Taiwan. Through a 2-year period of review, discussion, and integration, a 9-chapter guideline was published in June 2007. In summary, our experience and process for management of TBI in Taiwan can be used as a reference for other developing countries.

Intracranial pressure fluctuation during hemodialysis in renal failure patients with intracranial hemorrhage.

Coagulopathy in renal failure patients often makes them vulnerable to intracranial hemorrhage. Emergency decompression to remove the hematoma and to stop bleeding is always indicated. After the surgery, hemodialysis (HD) should be arranged to maintain the BUN/Cr. level, and I/O balance. During HD, intracranial pressure in all of the patients in this study fluctuated. This phenomenon always resulted in neurological deterioration in acute or chronic renal failure. We present intracranial pressure (ICP) changes during HD in five acute or chronic renal failure patients with intracranial hemorrhage. They all underwent craniectomy or craniotomy with ICP monitors implantation. Different HD protocols were arranged for these patients and then we observed clinical results. ICP elevated during HD and resulted in severe brain swelling. This situation was one of the clinical presentations of dialysis disequilibrium syndrome (DDS). Four patients died because of this complication and one survived. ICP fluctuation seemed to be correlated with the fluid amount and frequency of HD. The prevalence and pathophysiology of DDS remain unclear. Renal failure patient with intracranial hemorrhage may be complicated with DDS when HD was performed. An attempt to reduce the fluid amount and to increase the frequency of HD might help these patients.

Evaluation of optimal cerebral perfusion pressure in severe traumatic brain injury.

Traumatic brain injury (TBI) is a major cause of death and disability. In the 2000 guidelines, one of the suggestions for TBI treatment was to maintain cerebral perfusion pressure (CPP) < or = 70 mmHg. But in the 2003 guidelines, the suggestion was changed to < or = 60 mmHg. There have been some discrepancies of opinions about this recommendation in recent publications. In this study, we retrospectively reviewed 305 severe TBI (STBI) patients with Glasgow Coma Scales (GCS) < or = 8 between January 1, 2002 and March 31, 2003. The study group was stratified according to use or nonuse of intracranial pressure (ICP) monitoring, ICP levels, ages, and GCS levels in order to test the correlation between CCP and the prognosis. The patients < 50-year-old, with higher GCS level, with ICP monitoring, and with ICP levels < 20 mmHg had lower mortality rates and better prognosis (GOS) (p < 0.05 or 0.001). The patients in the GCS 3-5 subgroup had a significantly lower mortality and better prognosis if the CPP value was maintained higher than 70 mmHg (p < 0.05) The optimal CPP maintained < or = 60 mmHg did not fit in all STBI patients. Our study concludes that it is critical to maintain CPP substantially higher in lower GCS level patients.

Effect of hyperbaric oxygen on patients with traumatic brain injury.

Hyperbaric oxygen therapy (HBOT) is the medical therapeutic use of oxygen at a higher atmospheric pressure. The United States Food and Drug Administration have approved several clinical applications for HBOT, but HBOT in traumatic brain injury (TBI) patients has still remained in controversial. The purpose of our study is to evaluate the benefit of HBOT on the prognosis of subacute TBI patients. We prospectively enrolled 44 patients with TBI from November 1, 2004 to October 31, 2005. The study group randomly included 22 patients who received HBOT after the patients' condition stabilization, and the other 22 corresponding condition patients were assigned into the matched control group who were not treated with HBOT. The clinical conditions of the patients were evaluated with the Glasgow Coma Scale (GCS) and Glasgow Outcome Scale (GOS) before and 3 to 6 months after HBOT. The GCS of the HBOT group was improved from 11.1 to 13.5 in average, and from 10.4 to 11.5 (p < 0.05) for control group. Among those patients with GOS = 4 before the HBOT, significant GOS improvement was observed in the HBOT group 6 months after HBOT. Based on this study, HBOT can provide some benefits for the subacute TBI patients with minimal adverse side effects.

Hypofractionated CyberKnife stereotactic radiosurgery for acoustic neuromas with and without association to neurofibromatosis Type 2.

CyberKnife stereotactic radiosurgery (CKSRS) has been proved effective in treating intra-cranial lesions. To treat acoustic neuroma (AN) patients with or without neurofibromatosis Type 2 (NF2) associations, the functional preservation of hearing, trigeminal nerve, and facial nerve are important. Twenty-one patients were treated with hypofractionated CKSRS. Fourteen non-NF2 and seven NF2 patients were enrolled. Cranial nerve function, audiograms, and magnetic resonance images (MRI) were monitored. Mean follow-up was 15 month. Tumors with volumes ranging from 0.13 to 24.8 cm3 (mean 5.4 cm3) were irradiated with the marginal dose 1800-2000 cGy/3 fractions. Tumors were treated with an 80 to 89% isodose line (mean 83%) and mean 97.9% tumor coverage. Two patients experienced hearing deterioration (16.7%) in the non-NF2 group, and 3 patients (50%) in the NF2 group. No facial or trigeminal dysfunction, brain stem toxicity, or cerebellar edema occurred. Tumor regression was seen in 9 patients (43%) and stable in 12 patients (57%). 100% tumor control rate was achieved. Hypofractionated CKSRS was not only effective in tumor control but also excellent in hearing preservation for non-NF2 AN. But for NF2 patients, although the tumor control was remarkable, hearing preservation was modest as in non-NF2 patients.

Factors predictive of fatality in massive middle cerebral artery territory infarction and clinical experience of decompressive hemicraniectomy.

To determine the factors predictive of fatality in massive middle cerebral artery (MCA) territory infarction and outcome of decompressive hemicraniectomy, 62 patients who were retrospectively verified with first event massive MCA infarctions were enrolled in this study. Amongst them, 21 received decompressive hemicraniectomy during hospitalization. Clinical data between early and late hemicraniectomy groups were also compared. Significant deterioration occurred in 40 cases, 21 of whom received decompressive hemicraniectomy. The other 19 received conservative treatment. The mortality rate of these 40 cases between decompressive hemicraniectomy and conservative treatment was 29% (six of 21) and 42% (eight of 19), respectively. Factors that predicted fatalities in our massive MCA infarction patients with or without decompressive hemicraniectomy were total scores of baseline GCS at the time of admission, associated with coronary artery diseases, and significant deterioration during hospitalization. This study confirms the lifesaving procedure of hemicraniectomy that prevents death in patients deteriorating because of cerebral edema after infarction, although it may produce severe disability with an unacceptably poor quality of life in survival. Despite high mortality and morbidity, decompressive hemicraniectomy to prevent cerebral herniation when significant deterioration is demonstrated are essential for maximizing the potential for survival.

Edematous necrosis in thiamine-deficient encephalopathy of the mouse.

Acute encephalopathy was produced in the adult male Swiss mouse by pyrithiamine injection in conjunction with a thiamine-deficient diet. The condition of some mice was reversed within 24 hours by a treatment of a high dose of thiamine. The lesions occurred selectively in the thalamus, pontine tegmentum, and mammillary body and were manifested by hemorrhage and edematous necrosis consisting of severe edema of astrocytes, myelin sheaths, and neuronal dendrites. Before thiamine treatment, these degenerative changes were not associated with any mesenchymal reaction. At 48 and 96 hours after thiamine treatment, these edematous changes persisted. Fat-laden macrophages appeared in the lesion. Some axons showed Wallerian-type degeneration. After three weeks of thiamine treatment, macrophages became thin and rod-shaped. Wallerian-type degeneration and myelin edema persisted. The oligodendrocytes and astrocytes were hypertrophic. These lesions of thiamine-treated encephalopathy of the mouse closely resembled the non-hemorrhagic lesions of human Wernicke encephalopathy. Mice which were concomitantly-induced with hyperglycemia and encephalopathy showed no significant differences in clinical and morphologic manifestations from the encephalopathic mice with normal blood sugar levels. Vascular permeability to horseradish peroxidase was increased only slightly at the initial stage, but was reversed in the mice which clinically responded quickly to thiamine treatment. Occasionally, persistent increase of permeability was seen in 21-day-old lesions. These findings suggested that, in thiamine-deficient encephalopathy, both nervous and vascular components in the brain were involved and that the morphologic manifestations of the nervous component were far more extensive than those of the blood vessels.

Evidence for a novel P2X purinoceptor in human placental chorionic surface arteries.

To characterize the P2x purinoceptor of arteries of human term placenta, a non-innervated organ, actions of ATP, alpha, beta-methylene-ATP and UTP on de-endothelialized chorionic surface artery segments were compared. ATP and alpha,beta-methylene-ATP caused reversible concentration-dependent contractions, but UTP elicited little or no contraction up to 517 microM. Concentration-effect curves to ATP and alpha,beta-methylene-ATP were parallel, and alpha,beta-methylene-ATP, EC50 4.2 +/- 1.2 microM, was 28-times as potent as ATP. At a saturating concentration, 103 microM, alpha,beta-methylene-ATP did not desensitize the ATP receptor. Contractions to ATP and alpha,beta-methylene-ATP were antagonized by 300 microM suramin. These findings indicate that P2X purinoceptors are present in placental chorionic surface arteries and that they differ from P2X purinoceptors in arteries of other tissues.

Morphometry of right ventricular papillary muscle in rat during development and regression of hypoxia-induced hypertension.

Morphometric analyses of the right ventricular papillary muscle, as well as measurements of right ventricular pressure and weight, were carried out in the rat during the development and recovery of hypoxic pulmonary hypertension. Animals were divided into hypoxic and normobaric control groups. The hypoxic rats were placed in hypobaric chambers for 1, 2, and 3 wks; and after 3 wks exposure, subgroups of hypoxic rats were allowed to recover in normoxia for 1 to 9 wks. Hematocrit (HCT) and right ventricular systolic pressure (RVSP) were measured prior to sacrifice. The heart was perfused, and the right ventricle (RV) was separated from the left ventricle and septum (LV+S) and weighed. The papillary muscles were dissected and processed for ultrastructural morphometry. Results showed that HCT, RVSP, and RV weight increased in the rats during the hypoxic exposure and then gradually returned to control levels after 3 to 4 wks of normobaric recovery. The papillary muscle of the hypoxic rats showed increased volume density of interstitium, increased diameter and cross sectional area of the cardiac myocytes, reduced volume density of mitochondria, and reduced mitochondria to myofilament ratio. During normoxic recovery, these morphometric indices returned toward control values at various periods of time ranging from less than 3 wks to 9 wks. The results indicate that the adaptive ultrastructural changes of the papillary muscle in RV hypertrophy paralleled the RVSP changes, and also demonstrate the reversibility of these changes in ambient oxygen.

Practical optoelectronic neural network realizations based on the fault tolerance of the backpropagation algorithm.

This paper describes how the fault tolerance of the backpropagation algorithm can be used to accommodate the realistic (nonideal) transfer characteristics of the optical communication links used, between neural layers, in optoelectronic neural networks. In particular the authors demonstrate that networks, utilizing MSM (metal-semiconductor-metal) photodiodes (PDs) and either LED (light emitting diode) or MQW (multiple quantum well) laser transmitters within these intraneural links, are capable of performing satisfactorily even in the presence of such nonideal device phenomena as: 60% optical crosstalk, 50% optoelectronic device variation, or a thresholded (I(th)=0.5*I(max)) laser output characteristic. Subsequent to this, the authors then show how it is possible to use this fault tolerance to simplify the neuron architecture, to the extent that it consists only of MSM PDs a current amplifier, and an MQW laser. The overall neuron transfer function is then a first-order approximation to the original sigmoidal function.

Combined ventriculoperitoneal shunt blockage, viscus perforation and migration into urethra, presenting with repeated urinary tract infection.

We present an extremely rare case of delayed and combined ventriculoperitoneal shunt blockage, viscus perforation and migration into the urethra manifested by a repeated urinary tract infection. This was discovered six months after the shunt was inserted. Although there were various other transient symptoms, the patient did not show obvious peritoneal signs. This complication could have been lethal if the discovery had been delayed. One of the best ways of preventing such migration is possibly the use of a softer catheter. However, making sure of appropriate redundancy for the abdominal part of the catheter may be of equal importance.

CC-chemokine ligand 18/pulmonary activation-regulated chemokine expression in the CNS with special reference to traumatic brain injuries and neoplastic disorders.

Pulmonary activation-regulated chemokine (PARC) now designated CC-chemokine ligand 18 (CCL18) has been shown to play a significant role in the pathogenesis of various tissue injuries and diseases in a proinflammatory or immune suppressive way to limit or support the inflammation or disease. While much is known about the roles of CCL18/PARC in non-neural tissues, its expression in the CNS has remained largely unexplored and controversial. Using reverse transcription polymerase chain reaction (RT-PCR) and double immunohistochemical staining, we analyzed the expression of CCL18/PARC in the human brain with special reference to traumatic brain injuries and tumors. The RT-PCR analysis revealed the expression of CCL18/PARC mRNA both in the traumatic brain and glioma tissues examined. Immunoexpression of CCL18/PARC protein was consistently detected in all cases of traumatic brain injuries examined by immunohistochemical staining. Double immunofluorescence labeling has extended the study that CCL18/PARC positive cells were macrophages/microglia, astrocytes or neurons. The CCL18/PARC expression was localized in macrophage-like cells in two of eight glioblastoma tissues whose cancer cells were CCL18/PARC negative. Unexpectedly, CCL18/PARC mRNA weakly and constitutively expressed by glioblastoma cell line was upregulated after endotoxin stimulation. The present results indicated a significant production of CCL18/PARC in different CNS traumatic and neoplasm tissues by specific cellular elements expressing the chemokine. An anti-inflammatory mechanism jointly exerted by these cells via CCL18/PARC may be involved in the CNS immunity after traumatic injury and tumorigenesis.

Electroporative alpha-MSH gene transfer attenuates thioacetamide-induced murine hepatic fibrosis by MMP and TIMP modulation.

Hepatic fibrosis represents a process of healing and scarring in response to chronic liver injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a 13-amino-acid peptide with potent anti-inflammatory effects. We have previously demonstrated that alpha-MSH gene therapy protects against thioacetamide (TAA)-induced acute liver failure. Therefore, the aim of this study is to investigate whether alpha-MSH gene therapy possesses antihepatic fibrogenic effect. Liver fibrosis was induced by long-term TAA administration in mice. alpha-Melanocyte-stimulating hormone expression plasmid was delivered via electroporation after liver fibrosis was established. Our results showed that alpha-MSH gene therapy attenuated liver fibrosis in TAA-treated mice. Reverse transcription polymerase chain reaction revealed that alpha-MSH gene therapy attenuated the liver transforming growth factor-beta1, collagen alpha1 and cell adhesion molecule mRNA upregulation. Following gene transfer, the expression of alpha-smooth muscle actin and cyclooxygenase-2 were both significantly attenuated. Further, alpha-MSH significantly increased matrix metalloproteinase (MMP), while tissue inhibitors of matrix metalloproteinase (TIMPs) were inactivated. In summary, alpha-MSH gene therapy reversed established liver fibrosis in mice and prevented the upregulated fibrogenic and pro-inflammatory gene responses after TAA administration. Its collagenolytic effect might be attributed to MMP and TIMP modulation. Hence, alpha-MSH gene therapy may be an effective therapeutic modality against liver fibrosis with potential clinical use.

Fine structure of tracheo-bronchial epithelial nerves of the cat.

The nerves in and immediately under the epithelial layer of the trachea and primary bronchi of the cat are studied with the electron microscope. The axons are unmyelinated and contain microtubules and mitochondria. Epithelial axons are observed throughout the entire epithelial layer, but, are usually concentrated in the basal area immediately above the basal lamina. Most axons are near the basal cells; others are in the vicinity of granulated cells or occur in the intercellular spaces between other columnar cells. A few of the epithelial axons are large and crowded with axoplasmic mitochondria. The possibility that some epithelial axons may have sensory functions is discussed.

Development of neuroepithelial bodies in pre- and postnatal mouse lungs: scanning electron microscopic study.

The development of pulmonary neuroepithelial bodies (NEBs) in pre- and postnatal mice were studied with scanning electron microscope. In the fetuses, at 17 days' gestation, the NEBs were recognized as slight epithelial elevations covered by developing Clara cells. At 18 days, the small apical surfaces of the specialized cells began to be exposed to the bronchiolar lumen. At 19 days (full term), numerous microvilli-covered surfaces of the specialized cells were located between the dome-shaped Clara cells. At this stage, the boundary of the NEBs was well outlined by the developing ciliated cells. In the postnatal animals, the surface structure of the specialized cells remained the same as that of the 19-day fetuses, but the modified Clara cells gradually became wide and flat. In older mice, some NEBs formed obvious spherical mounds projecting into the bronchiolar lumen. The rapid differentiation of the microvillar projections on the surfaces of the specialized cells shortly before birth should provide the animals ample surface area to make contact with the airway contents.

Innervation of rabbit fetal lungs.

Nerve fibers, autonomic ganglia, and neuroepithelial bodies of the lungs of rabbit fetuses, 17 to 31 days gestational age, were studied with neurohistological techniques including silver impregnation, acetylcholinesterase histochemistry, and glyoxylic-acid-induced histofluorescence for monoamines. The silver impregnation method showed that nerve fibers and ganglia accompanied the bronchi and large pulmonary blood vessels to enter the developing lungs by the 17th day of gestation. Cholinergic and adrenergic nerves began to appear in the walls of the bronchi on the 21st day. The developing pulmonary arteries had accompanying adrenergic nerves on the 25th day. Acetylcholinesterase-positive parasympathetic ganglia were seen on the 27th day. Silver-impregnated nerve fibers in the developing alveolar walls and pleura were found on the 25th day. Neuroepithelial bodies and specialized single cells which were argyrophilic, acetylcholinesterase-positive, and fluorescent could be demonstrated in 19--21-day-old and older fetuses; and some of these structures were innervated by sensory and autonomic motor fibers. These observations indicated that nervous tissue and neuroepithelial bodies appeared in the lungs during the glandular stage of the lung development and that differentiation of adrenergic and cholinergic nerves began in the late glandular stage.

Electron-microscopic studies of the innervation of the pulmonary veins of the mouse.

The innervation of the pulmonary veins was studied with electron microscopy. The adrenergic and cholinergic nerves were differentiated with potassium permanganate fixation. All three layers of the venous wall, namely, the tunica intima, media and adventitia, contained unmyelinated axons. Adrenergic and cholinergic axons were located near the cardiac muscle in the tunica media and near the smooth muscle in the tunica intima. The morphological relationships may explain the pharmacological and electrophysiological responses of the large pulmonary veins observed by others.

Ultrastructural evidence for the innervation of human pulmonary alveoli.

Electron Microscopic observations of the biopsied human pulmonary alveoli showed the occurrence of unmyelinated axons in the interstitium near the type I pneumocytes. These axons very likely have sensory functions.