原发性松果体区胚胎癌的诊断与治疗(附二例报告及文献复习)

Objective Primary embryonal carcinoma in pineal region is extremely rare Here we report two such cases and combined literatures review to discuss its diagnosis, treatment and prognosis. Method Two primary embryonal carcinoma in pineal region verified histologically were presented. In one cases, the preoperative serum alpha - fetoprotein (AFP) level reached significantly high level, 6 810μg/L, but showed negative staining forβ-human chorionic gonadotropin (β- HCG) . In the other one, accompanied by elevation of β-HCG level, 5 260 mIU/ml, the serum AFP was negative. The tumors were microsurgically removed by transeccipito-tentorial approach. Endoscopic third ventriculostomy was used after tumor removal because of recurrent hydrocephalus. Both patients received adjunctive treatments included radiation therapy (whole central nervous system 30 Gy and tumor bed 50 Gy) and 4 course of chemotherapy. Results In both patients, the tumors were totally removed. Postoperative tumor immunohistochemistry indicators were present in case 1 with positive reaction for cytokeratin(CK) and AFP, in case 2 with positive CK and β - HCG. After adjunctive treatments, the serum AFP and β - HCG of two patiants were decreased to normal ranges. After post - operative follow - up of one year,two patients still survived and the serum markers were almost normal. Conclusions Measurement of serum β-HCG and AFP is extraordinarily significant for the diagnosis and post - treatment monitoring of pineal region embryonal carcinoma. Pathological differential diagnosis requires immunohistochemical indicators including cytokeratin (CK),AFP andβ- HCG. With radically surgical removal and combined adjunctive therapy including radiation and chemotherapy, good consequence could be obtained.     

原发性松果体区胚胎癌的诊断与治疗(附二例报告及文献复习)

目的 原发性松果体区胚胎癌非常罕见,本文报道2例,并结合文献探讨其诊断、治疗和预后.方法 2例经病理证实的原发性松果体区胚胎癌,术前例1患者血清甲胎蛋白(AFP)6 810μg/L,人绒毛膜促性腺激素(β-HCG)正常,例2患者血清AFP正常,β-HCG 5 260 mIU/ml.采用枕部经小脑幕入路显微手术切除肿瘤,术后联合放化疗.结果 2例患者肿瘤均达到镜下全切,术后肿瘤免疫组化示例1:CK、AFP阳性;例2:CK、β-HCG阳性.经放化疗后,血清AFP/β-HCG基本正常.术后1年随访2例患者仍然存活.结论 血清AFP、β-HCG对胚胎癌的诊断及预后判断有重要作用,免疫组化指标CK、AFP、β-HCG对病理诊断有鉴别意义,该病采用手术联合放化疗的综合疗法,可获得较好疗效.

Abstract：

Objective Primary embryonal carcinoma in pineal region is extremely rare Here we report two such cases and combined literatures review to discuss its diagnosis, treatment and prognosis. Method Two primary embryonal carcinoma in pineal region verified histologically were presented. In one cases, the preoperative serum alpha - fetoprotein (AFP) level reached significantly high level, 6 810μg/L, but showed negative staining forβ-human chorionic gonadotropin (β- HCG) . In the other one, accompanied by elevation of β-HCG level, 5 260 mIU/ml, the serum AFP was negative. The tumors were microsurgically removed by transeccipito-tentorial approach. Endoscopic third ventriculostomy was used after tumor removal because of recurrent hydrocephalus. Both patients received adjunctive treatments included radiation therapy (whole central nervous system 30 Gy and tumor bed 50 Gy) and 4 course of chemotherapy. Results In both patients, the tumors were totally removed. Postoperative tumor immunohistochemistry indicators were present in case 1 with positive reaction for cytokeratin(CK) and AFP, in case 2 with positive CK and β - HCG. After adjunctive treatments, the serum AFP and β - HCG of two patiants were decreased to normal ranges. After post - operative follow - up of one year,two patients still survived and the serum markers were almost normal. Conclusions Measurement of serum β-HCG and AFP is extraordinarily significant for the diagnosis and post - treatment monitoring of pineal region embryonal carcinoma. Pathological differential diagnosis requires immunohistochemical indicators including cytokeratin (CK),AFP andβ- HCG. With radically surgical removal and combined adjunctive therapy including radiation and chemotherapy, good consequence could be obtained.     

Microsurgical resection of ventral foramen magnum meningiomas via a far-lateral suboccipital approach

BACKGROUND: In recent years some reports have been published propagating microsurgical resection of ventral foramen magnum meningiomas (VFMMs). Operative approaches to these lesions have been studied by various authors, but remain controversial. OBJECTIVE: To discuss the operative technique and outcome in patients with VFMMs who had been treated via a far lateral suboccipital approach. DESIGN: Retrospectively clinic case investigation. SETTING: Department of Neurosurgery, the Ninth People's Hospital, Medical School of Shanghai Jiao Tong University. PARTICIPANTS: Between January 1997 and June 2003, 10 patients were treated surgically with VFMMs in Department of Neurosurgery, the Ninth People's Hospital, Medical School of Shanghai Jiao Tong University. In the series of 10 patients, ages ranged from 37 to 72 years, mean (53±10) years, were consisted of 6 males and 4 females. All the subjects were informed of the treatment plan and agreed to join the experiment. Early symptoms included headache and upper cervical pain. The time between the first occurrence of symptoms and the diagnosis ranged from 6 months to 17 months, mean (10.3±3.4) months. Main presenting symptoms were unilateral upper extremity sensory and motor deficits in 6 cases, swallowing difficulties in 2 and spastic quadriparesis in 2. VFMMs were demonstrated as round by the computed tomographic (CT) scan and magnetic resonance imaging (MRI) in all patients. The maximum diameter of tumors ranged from 2 to 4 cm, mean (2.55±0.57) cm, including 2 cm in one case, 2.0-3.0 cm in six and 3.0-4.0 cm in three. METHODS: ①All tumors were removed via the far lateral suboccipital approach. Resection of the posterior 5 mm of the condyle was necessary in one patient whose tumors' diameter were 2 cm. The patient was situated in the lateral decubitus position. The head was fixed in a Mayfield headrest. A C-shaped incision made behind the ear 2 cm medial to the mastoid process, turning vertically down to the level C4, to expose the extradural segment of the vertebral artery (VA). After the dura was opened longitudinally behind VA entry point, the tumor was revealed to identify the complete cranial nerves and the intracranial VA under magnification of the surgical microscope. Every attempt should be made to keep the arachnoid and the dentate ligament was sectioned. Then the tumor was debulked significantly, and dissected away from the cranial nerves and the blood vessels with microsurgical techniques. If it was risk to dissect tumor from the vertebral artery, its branches, or any cranial nerve, the progression was discontinued and portion of the tumor was left behind. After resection of the tumor, the site of its attachment was coagulated and the involved layer of dura was resected. ②The degree of tumor resection was classified based on Al-Mefty's grade into three categories: gross-total resection: excision of the dural attachment and drilling of adjacent bone; near-total resection: a few millimeters of insulated and cauterized tumor were left on the vertebral artery or other vital; subtotal resection: more than 50% of the tumor mass were removed. ③All patients underwent clinical examination for lower cranial nerves or long tract deficits on the first day postoperatively. CT or MRI and neurological examinations were performed at 3 months of follow-up. MAIN OUTCOME MEASURES: Operative effect. RESULTS: All ten patients with VFMMs were treated via a far lateral suboccipital approach. Gross total resection was achieved in 6 patients, near-total resection was carried out in 2 and subtotal resection in 2 patients. One patients died in the postoperative period due to acute respiratory distress syndrome, five patients kept normal neurological status, whereas other four patients suffered from lower cranial nerve deficits and aspiration pneumonia was observed in two of them. The data of following up for 3 months showed that 2 patients still had lower cranial nerve deficit and others recovered from their illness. No tumor relapse or increment was found in CT or MRI scans. CONCLUSION: Most of VFMMs could be totally removed via a far lateral suboccipital approach with or without resection of the occipital condyle according to the tumor size, allowing most of these patients to achieve a good outcome in a 3 months follow-up.     

Levels of soluble delta-like ligand 1 in the serum and cerebrospinal fluid of tuberculous meningitis patients

In this study,the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum of 50 patients with tuberculous meningitis,30 patients with viral meningitis,20 patients with purulent meningitis and 40 subjects without central nervous system disease were determined using an enzyme-linked immunosorbent assay.The mean levels of soluble delta-like ligand 1 in both cerebrospinal fluid and serum from patients with tuberculous meningitis were significantly higher compared with those from patients with viral meningitis or purulent meningitis or from subjects without central nervous system disease.Meanwhile,the level of soluble delta-like ligand 1 gradually decreased as tuberculous meningitis patients recovered.If patients deteriorated after treatment,the level of soluble delta-like ligand 1 in cerebrospinal fluid gradually increased.There was no correlation between the level of soluble delta-like ligand 1 and the protein level/cell number in cerebrospinal fluid.Our findings indicate that the levels of soluble delta-like ligand 1 in cerebrospinal fluid and serum are reliable markers for the diagnosis of tuberculous meningitis and for monitoring treatment progress.At the same time,this index is not influenced by protein levels or cell numbers in cerebrospinal fluid.     

Serum alkaline phosphatase and γ-glutamyl transpeptidase levels in patients with neuromyelitis optica and multiple sclerosis

Objective To investigate the serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) levels in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS).Methods Serum ALP and GGT levels in patients with NMO and MS from the database of demyelinating diseases in our hospital were analyzed.Eighty-five healthy controls were chosen.The differences of serum ALP and GGT levels in patient groups and controls were compared, and the correlations between clinical features (age of the subjects, course of disease, times of relapse and scores of EDSS) and both ALP and GGT levels were analyzed. Results The serum ALP and GGT levels in patients with NMO were significantly higher than those in patients with MS and the controls (P<0.05).Patients with NMO still had significantly higher serum ALP level in acute phase than patients with MS,and the serum ALP levels in male patients with NMO and the serum GGT levels in female patients with NMO were, respectively,statistically higher than that of male patients with MS and female patients with MS (P<0.05). In patients with NMO, significantly positive correlations between serum GGT level and both age and times of relapse were noted (P<0.05). Conclusion Serum ALP and GGT levels differ in patients with NMO and MS, indicating their differential diagnostic value in NMO and MS to certain extent.     

Serum alkaline phosphatase and γ-glutamyl transpeptidase levels in patients with neuromyelitis optica and multiple sclerosis

Objective To investigate the serum alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) levels in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS).Methods Serum ALP and GGT levels in patients with NMO and MS from the database of demyelinating diseases in our hospital were analyzed.Eighty-five healthy controls were chosen.The differences of serum ALP and GGT levels in patient groups and controls were compared, and the correlations between clinical features (age of the subjects, course of disease, times of relapse and scores of EDSS) and both ALP and GGT levels were analyzed. Results The serum ALP and GGT levels in patients with NMO were significantly higher than those in patients with MS and the controls (P<0.05).Patients with NMO still had significantly higher serum ALP level in acute phase than patients with MS,and the serum ALP levels in male patients with NMO and the serum GGT levels in female patients with NMO were, respectively,statistically higher than that of male patients with MS and female patients with MS (P<0.05). In patients with NMO, significantly positive correlations between serum GGT level and both age and times of relapse were noted (P<0.05). Conclusion Serum ALP and GGT levels differ in patients with NMO and MS, indicating their differential diagnostic value in NMO and MS to certain extent.     

Serum anti-aquaporin 4 antibody in neuromyelitis patients is not correlated with the length of injured spinal cord segments

Clinical information and serum samples of 20 neuromyelitis patients and 30 patients with multiple sclerosis were collected in this study. The expression of anti-aquaporin 4 antibody in the serum of all patients was detected with an indirect immunofluorescence assay, using human embryonic kidney 293 cell line that stably express human-derived aquaporin 4 as a substrate. The characteristics of head and spinal magnetic resonance imaging were also observed in patients who had neuromyelitis and were positive for anti-aquaporin 4 antibody. Results showed that the expression of anti-aquaporin 4 antibody was significantly different between multiple sclerosis patients and neuromyelitis patients. There were 13 out of 20 neuromyelitis patients (including high-risk syndrome) that were positive for anti-aquaporin 4 antibody. The magnetic resonance imaging examinations of the head and spinal cord found that among the 13 positive patients, nine cases showed normal cerebral hemisphere and optic nerve, two cases had optic nerve changes, and one case had an atypical lesion in the brain. All 30 multiple sclerosis patients were negative for this antibody. The experimental findings indicate that patients with neuromyelitis optica had more than three lesioned segments in the spinal cord by magnetic resonance imaging, and the segment length of the injured spinal cord was not associated with the titer of aquaporin 4 antibody in neuromyelitis patients.     

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord： Analysis of 21 cases

BACKGROUND： Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE： To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN： Case analysis. SETTING： Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS： A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5 - 108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS： Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187 - 1 059 ng/L and normal value of serum homocysteine was 5 - 15μ mol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES： （1） Levels of blood routine, serum vitamin B12 and homocysteine; （2） results of neuroelectrophysiological examination; （3） results of MRI examination of spinal cord; （4） prognosis. RESULTS： Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. （1） Clinical manifestations： All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs （5 cases）, unstable gait （3 cases）, limb asthenia （4 cases）, limb numbness combined with light asthenia （5 cases）, limb numbness combined with unskillful activity （3 cases）, and limb numbness combined with unstable gait （1 case）. （2） Experimental results： Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of bomocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. （3） Results of neuroelectrophysiological examination： Among all patients, 95% （20/21） patients had abnormal sensory-evoked potential, 89% （8/9） patients had abnormal motor evoked potential, 67% （10/15） patients had abnormal nerve conduction, 13% （2/15） patients had neurogenic muscle injury showed by electromyography （EMG）, 70% （7/10） patients had abnormal brain-stem auditory evoked potential, and 40% （4/10） patients had abnormal visual evoked potential. （4） Results of MRI examination of spinal cord： MRI examination demonstrated that 40% （6/15） patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B I2 therapy. CONCLUSION： Nervous system lesion caused by vitamin B 12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin BI2. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.     

Diagnosis and clinical manifestations of subacute combined degeneration of the spinal cord: Analysis of 21 cases

BACKGROUND: Subacute combined degeneration of the spinal cord is caused by vitamin B12 deficiency and is a kind of degenerative disease owing the characteristics of nervous system diseases. In addition, different patients have variously clinical manifestations and various prognoses after vitamin B12 therapy. OBJECTIVE: To investigate and analyze diagnosis, clinical manifestations and prognosis of subacute combined degeneration of the spinal cord. DESIGN: Case analysis. SETTING: Department of Neurology, the Third Hospital of Peking University. PARTICIPANTS: A total of 21 subacute combined degeneration of the spinal cord patients including 14 males and 7 females aged from 33 to 82 years were selected from Department of Neurology, the Third Hospital of Peking University from January 1999 to December 2005. Duration from onset to final diagnosis lasted for 1.5–108 months. All patients had typically clinical manifestations; meanwhile, level of serum vitamin B12 was decreased and/or vitamin B12 therapy was effective. All patients provided the confirmed consent. METHODS: Clinical data of 21 subacute combined degeneration of the spinal cord patients were retrospectively analyzed, while general data and clinical characteristics were recorded at the same time. Levels of blood routine, serum vitamin B12 and homocysteine were measured at the phase of hospitalization. Normal value of serum vitamin B12 was 187–1 059 ng/L and normal value of serum homocysteine was 5–15 μmol/L. All patients received neuroelectrophysiological examination and 15 patients received MRI examinations of spinal cord. After final diagnosis, patients were given vitamin B12 therapy. And follow-up was performed to investigate the prognosis. MAIN OUTCOME MEASURES: ① Levels of blood routine, serum vitamin B12 and homocysteine; ② results of neuroelectrophysiological examination; ③ results of MRI examination of spinal cord; ④ prognosis. RESULTS: Clinical data of 21 patients and follow-up data of 20 patients were involved in the final analysis and 1 patient was lost because of living in the other province. ① Clinical manifestations: All 21 patients had typically clinical manifestations. The original symptoms included numbness of lower and/or upper limbs (5 cases), unstable gait (3 cases), limb asthenia (4 cases), limb numbness combined with light asthenia (5 cases), limb numbness combined with unskillful activity (3 cases), and limb numbness combined with unstable gait (1 case). ② Experimental results: Eight subacute combined degeneration of the spinal cord patients accompanied with mild-severe anemia and mean corpuscular volume of 13 patients were increased. Among 13 subacute combined degeneration of the spinal cord patients not administrating vitamin B12 before hospitalization, the levels of serum vitamin B12 of 2 patients were not measured but those of other patients were decreased. After vitamin B12 therapy,the levels of serum vitamin B12 of 8 patients were normal or increased. In addition, the levels of serum homocysteine of 6 patients were not measured but those of 7 patients were increased. While, the levels of homocysteine of 5 following-up patients were normal. The levels of serum vitamin B12 of 8 patients who received with vitamin B12 therapy before hospitalization were normal or increased. Among them,the levels of homocysteine were not measured in 4 patients, those of 3 patients were increased, and that of 1 patient was normal. ③ Results of neuroelectrophysiological examination: Among all patients, 95% (20/21) patients had abnormal sensory-evoked potential, 89% (8/9) patients had abnormal motor evoked potential, 67% (10/15) patients had abnormal nerve conduction, 13% (2/15) patients had neurogenic muscle injury showed by electromyography (EMG), 70% (7/10) patients had abnormal brain-stem auditory evoked potential, and 40% (4/10) patients had abnormal visual evoked potential. ④ Results of MRI examination of spinal cord: MRI examination demonstrated that 40% (6/15) patients had spinal cord lesion, but spinal cord lesion disappeared in 2 patients during follow up. In addition, clinical manifestations of patients were improved after standard vitamin B12 therapy. CONCLUSION: Nervous system lesion caused by vitamin B12 deficiency is not only involved in spinal cord, also in peripheral nerve, optic nerve, auditory pathway, etc. Diagnosis of the lesion depends on clinical characteristics and level of serum vitamin B12. Especially, neuroelectrophysiological examination, measurement of homocysteine and MRI examination of spinal cord are beneficial for diagnosis and evaluation of therapeutic effects.     

Clinical manifestation, imageological and pathological characteristics of Wernicke encephalopathy

BACKGROUND: The clinical manifestations of Wernicke encephalopathy(WE) are atypical and short of effective auxiliary examination means. The effects of magnetic resonance imaging (MRI) in the diagnosis of WE have been reported successively. But its imageological detection needs to be further investigated. OBJECTIVE: To analyze the characteristics of clinical manifestations, skull MRI examination and pathological results in patients with WE. DESIGN: Retrospective analysis. SETTING: The General Hospital of Chinese PLA. PARTICIPANTS: Ten patients of WE admitted to the Department of Neurology, General Hospital of Chinese PLA were recruited. Among them, five patients were diagnosed pathologically after death. Their pathological changes accorded with the pathological characteristics of WE. The other 5 patients were diagnosed clinically before death. Their pathological changes accorded with clinical and imageological manifestations and had definite reaction to the treatment of thiamine. Ten patients, 7 males and 3 females, were aged (47±13) years ranging from 33 to 73 years. Their disease courses averaged 6 weeks ranging from 3 to 10 weeks. They all were non-alcoholics. Four patients developed WE after acute pancreatitis, two patients after the recurrence of gastric cancer, two patients after cholecystectomy, one patient after hepatitis medicamentosa, one patient after Alzheimer disease. Informed consents were obtained from all the patients and their relatives. METHODS: After admission, clinical manifestations of patients were observed and recorded. Five patients underwent skull MRI examination and their detected results were recorded. Five dead patients underwent autopsy and brain pathological examinations. Neuropathological examination involved cerebrum, cerebellum and brain stem. MAIN OUTCOME MEASURES: Clinical manifestations, MRI examination results, pathological analysis results and prognosis of all the patients. RESULTS: Ten patients with WE were involved in the final analysis. ①Nine patients presented various degrees of mental and conscious disturbance. Six patients initially presented vertigo, nausea, and vomiting. Five patients showed opthalmoplegia. Three patients presented hypotension (BP < 120/60 mm Hg, 1 mm Hg= 0.133 kPa). Two patients showed ataxia. One patient showed severe polyneuropathy. Both lower extremities were more severe. EMG showed axonal degeneration. ②Five patients accepted skull MRI examination. Three patients showed typical high signals in periaqueductal regions and circumference of third and fourth ventriculus in T2 -weighted and flair-weighted images, two of them showed high signals in fornixes in T2 -weighted and flair-weighted images, and one of them showed high signals in optic chiasma, both mammillary bodies, and subcortical white matter. No abnormality was found in the other two patients. Two patients who accepted the supplements of thiamine showed obviously improvements in the second MRI examination. ③Macroscopically, the border between gray and white matters was clear in the coronal section of cerebrum. Congestions, edema and multiple petechial hemorrhages were found in periaqueductal regions, circumference of third and fourth ventriculus, and both mammillary bodies. Microscopically, various degrees of necrosis of parenchymal structures, loss of nerve cells and ischemic changes were found. Myelinated fibers were more affected than neurons. There were focal capillary proliferation and multiple petechial hemorrhages. Prominent astrocytic proliferations were found in gelatinous fiber staining. And demyelinations were found in myelin staining. These pathological findings were all in accord with the diagnostic criteria of WE. ④In the diagnosis before death, 4 of 5 patients who were supplemented with thiamine had obvious improvement 2 weeks later and 1 of them abandoned therapy due to progressive aggravation of jaundice caused by recurrence of stomach cancer. The other 5 patients who were not diagnosed definitely before death and not supplemented with thiamine died. Final diagnosis was performed in autopsy examination. CONCLUSION: The clinical manifestations of this group of WE patients are atypical. MRI and pathological examination results are corresponding, and both have the characteristic manifestations of WE..     

The neuroendocrinology of stress and the pathophysiology and therapy of depression and anxiety

Clinical and preclinical studies have gathered substantial evidence that stress response alterations play a major role in the development of major depression, panic disorder, and post-traumatic stress disorder. The stress response, the hypothalamic pituitary adrenocortical (HPA) system and its modulation by corticotropin-releasing hormones (CRH),corticosteroids,and their receptors, and the roles of natriuretic peptides and neuroactive steroids are described. We review the role of the HPA system in major depression, panic disorder, and post-traumatic stress disorder and its possible relevance for treatment. Impaired glucocorticoid receptor function in major depression is associated with an excessive release of neurohormones such as CRH, to which a number of signs and symptoms characteristic of depression can be ascribed. In panic disorder, a role of central CRH in panic attacks has been suggested. Atrial natriuretic peptide (ANP) is causally involved in sodium lactate-induced panic attacks. Furthermore, preclinical and clinical data on its anxiolytic activity suggest that nonpeptidergic ANP receptor ligands may be potentially useful in the treatment of anxiety disorders. Post-traumatic stress disorder is characterized by a peripheral hyporesponsive HPA system and elevated CRH concentrations in the CSF. This dissociation is probably related to an increased risk of this disorder. We further review recent data that describe an important role of GABA(A)-receptor modulatory,3 alpha-reduced neuroactive steroids in major depression, anxiety, and its treatment. Antidepressants are effective in both depression and anxiety disorders and have major effects on the HPA system,especially on glucocorticoid and mineralocorticoid receptors. Normalization of HPA system abnormalities is a strong predictor of the clinical course, at least in major depression and panic disorder. Currently,CRH-R1 or glucocorticoid receptor antagonists and ANP receptor agonists are being studied and may provide future treatment options more closely related to the pathophysiology of these disorders.     

Polymorphisms of DRD4 and DRD3 and risk of avoidant and obsessive personality traits and disorders

We investigated whether polymorphisms of the dopamine D4 receptor (DRD4) and polymorphisms of the dopamine D3 receptor (DRD3) were associated with personality disorder symptomatology rather than with personality traits such as novelty seeking. DNA was obtained from 145 depressed patients in a clinical trial. These patients were assessed for the presence of personality disorder symptoms and disorders. The 2-repeat allele of the DRD4 exon III polymorphism was associated with increased rates of avoidant and obsessive personality disorder symptomatology. The T,T genotype of the DRD4 -521 C>T polymorphism was also associated with increased rates of avoidant and obsessive personality disorder symptomatology. The Gly9,Gly9 genotype of the DRD3 Ser9Gly polymorphism was associated with increased rates of obsessive personality disorder symptomatology. None of these three polymorphisms were associated with novelty seeking or other temperament traits on the Temperament and Character Inventory. Our results suggest that genetic polymorphisms of DRD4 and DRD3 may well be associated with personality traits, and that conflicting findings to date may arise from the problem of phenotype definition.     

沙盘游戏疗法在地中海贫血患儿心理干预中的应用

本文目的是对沙盘游戏疗法在地中海贫血患儿心理干预中的应用进行综述,以期为地中海贫血患儿的心理康复提供参考。地中海贫血是以珠蛋白生成障碍为主要特征的遗传性疾病,由于长期输血治疗,患儿存在较多的心理和行为问题。沙盘游戏疗法作为一种有效、实用的儿童心理治疗方法,对提高地中海贫血患儿的康复效果、改善生存质量有重要的临床意义。     

癫痫共病抑郁的机制及临床诊疗

本文目的是探讨癫痫共病抑郁的可能机制及临床诊疗。癫痫是一种常见的、慢性的、致残性的神经疾病,癫痫患者生活质量下降,存在明显的负性情绪,常伴发各种精神疾病。癫痫与抑郁具有共同的神经生物学基础,可能存在共同的发病机制。本文从癫痫共病抑郁的发病机制、临床诊断及治疗方面予以总结归纳。     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Modulators and inhibitors of gamma- and beta-secretases

Most gene mutations associated with Alzheimer's disease point to the metabolism of amyloid precursor protein as a potential cause. The beta- and gamma-secretases are two executioners of amyloid precursor protein processing resulting in amyloid-beta. Significant progress has been made in the selective inhibition of both proteases, regardless of structural information for gamma-secretase. Several peptidic and nonpeptidic leads were identified for both targets.