干眼的神经病理机制与针对性治疗

干眼(DE)是老年人主要眼科疾病之一,可引起疼痛和不适,且这些症状可持续存在,发展为慢性,从而显著影响患者的生活质量。DE症状包括伤害性症状与神经性症状,具体表现为干涩感、异物感、烧灼感等。DE的病理机制比较复杂,除了目前公认的泪液高渗、炎症与泪液分泌障碍外,心理因素的作用及神经高敏感性在DE的发生中也具有重要的意义,且是导致DE症状慢性化及引起恶性循环的原因。本文就DE的伤害性症状及神经性症状间的差异进行了分析,并针对DE的神经病理机制、症状评估与治疗进行了探讨与总结。

犬瘟热的神经性病理机制

犬瘟热病毒(Canine distemper,CDV)可以诱发犬产生严重的免疫抑制和神经性疾病,例如脱髓鞘脑脊髓炎(demyelinating leukoencephalitis,DL),脱髓鞘是具有代表性的神经性病症。犬瘟的神经病理机制研究发现,在脱髓鞘急性损伤期,少突胶质细胞代谢障碍及小胶质细胞活化;在脱髓鞘的慢性期,免疫系统逐渐恢复,在脱髓鞘斑区发生炎症,促使损伤的恶化。研究发现:犬瘟热病毒可以存在于炎性脱髓鞘损伤区外且逃避免疫识别,这是慢性炎症性脱髓鞘损伤的主要机制,而逃避免疫识别的机制是病毒的非溶细胞性的选择性传播及限制性的感染。

In vitro Study of Interstitial Combination Chemotherapy in the Treatment of Glioma

Objective： To investigate the inhibitory effects of combination chemotherapy of Carboplatin （CBP）, Teniposide （Vm-26）, Methasquin （MTX）, and Nimodipine （NIM） on glioma, and to explore the sensitivity of glioma cells to different treatment regimens so as to provide some clues for clinical usage of interstitial combination chemotherapy. Methods： MTT assay and 3H-TdR incorporation assay were performed to evaluate the inhibitory effects upon the proliferation of glioma cells, and to compare the sen- sitivity of glioma cells to administration of CBP, Vm-26, MTX, and NIM with that of the administration of CBP＋NIM, Vm-26＋NIM, MTX＋NIM, CBP＋Vm-26＋MTX, or CBP＋Vm-26＋MTX＋NIM, respectively. Results： The inhibition rate of CBP＋Vm-26＋MTX＋NIM combination administration against glioma cells was 96.64%, higher than that of CBP＋NIM （69.03%）, Vm-26＋NIM （71.53%）, MTX＋NIM （52.75%）, CBP＋Vm-26＋MTX （78.59%） （P〈0.01）, and the dosage of CBP, Vm-26, and MTX was declined to 1/10- 1/100 that of respective use of CBP, Vm-26, and MTX. Conclusion： The curative effect of combination administration of CBP, Vm-26, MTX, and NIM was much better than that of respective administration, suggesting a higher inhibition rate and a lower dosage use.

Therapeutic Effects of Stereotactic Radiotherapy on 389 Cases of Brain Glioma

Objective： To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods： From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic radiotherapy, among which 151 cases were treated by stereotactic radiosurgery （SRS） and the other 238 cases, by fractionated stereotactic radiotherapy （FSRT）. In the SRS group, the marginal tumor dose was 20 to 30 Gy （median, 2.6 Gy）. One to 6 isocenters （median, 2.48） and 5 to 21 irradiation arcs （median, 8.45） were applied. In the FSRT group, the per-fraction marginal tumor dose was 8 to 12 Gy with 1 to 6 isocenters （median, 2.53）, 6 to 20 irradiation arcs （median, 8.25） and 2-5 fractions delivered everyday or every other day. Results： Three months after treatment, the complete and partial response rates were 13.9% and 45.7% in SRS group respectively. The stable disease rate was 17.2%. The total effective rate was 76.8%. In FSRT group, the complete and partial remission rates were 19.7% and 47.9% respectively. The stable disease rate was 20.6%. The total effective rate was 88.2%. The total effective rate of FSRT group was higher than that in SRS group （X^2=9.874, P=0.020）. The 1-year, 3-year and 5-year survival rate of all patients was 54.3%, 29.3%, 16.5% respectively. The 1-year, 3-year and 5-year survival rate in SRS group and FSRT group was 52.3% vs 26.5%, 11.9% vs 55.5%, and 31.1 vs 19.3% respectively. There was no significant difference between the two groups （X^2=2.16, P=0.1417）. The brain edema caused by the main radiation was more severe in the SRS group than in FSRT group （X^2=4.916, P=0.027）. Conclusion： It is effective for brain glioma to be treated by stereotactic radiotherapy. Compared with SRS, the FSRT has the advantage of good effect and less side response.

Study of MR Imaging and MR Spectroscopy in the Diagnosis of Gliomatosis Cerebri

Objective： To evaluate retrospectively the MRI and MRS features of gliomatosis cerebri for investigating the clinical value of MR imaging and MR spectroscopy in the diagnosis of gliomatosis cerebri. Methods： Seven patients with gliomatosis cerebri proved clinically and histopathologically were analyzed retrospectively. All patients underwent MRI and three of them underwent MRS. Results： The tumors involved at least 2 cerebral lobes in all patients, with low signal intensity on TlWI and high intensity on T2WI. The area invaded by tumor showed cortex swelling and no obvious mass effect. The tumors presented small nodules or plaque lesions on enhance-MRI in 3 cases, and no contrast enhancement was shown in the rest 4 cases. All patients with MRS showed elevated Cho, Cho/Cr and Cho/NAA levels as well as varying degrees of decreased NAA. Conclusion： MRI is the method of first choice to detect gliomatosis cerebri so far, MR spectroscopy might be helpful in its differential diagnosis.

Early diabetic neuropathy:Triggers and mechanisms

Pedpheral neuropathy, and specifically distal peripheral neuropathy （DPN）, is one of the most frequent and troublesome complications of diabetes mellitus. It is the major mason for morbidity and mortality among diabetic patients. It is also frequently associated with debilitating pain. Unfortunately, our knowledge of the natural history and pathogenesis of this disease remains limited. For a long time hyperglycemia was viewed as a major, if not the sole factor, responsible for all symptomatic presentations of DPN. Multiple clinical observations and animal studies supported this view. The control of blood glucose as an obligatory step of therapy to delay or reverse DPN is no longer an arguable issue. However, while supporting evidence for the glycemic hypothesis has accumulated, multiple controversies accumulated as well. It is obvious now that DPN cannot be fully understood without considering factors besides hyperglycemia. Some symptoms of DPN may develop with little, if any, correlation with the glycemic status of a patient. It is also dear that identification of these putative non-glycemic mechanisms of DPN is of utmost importance for our understanding of failures with existing treatments and for the development of new approaches for diagnosis and therapy of DPN. In this work we will review the strengths and weaknesses of the glycemic hypothesis, focusing on dinical and animal data and on the pathogenesis of early stages and triggers of DPN other than hyperglycemia.

Slow transit constipation: A functional disorder becomes an enteric neuropathy

Slow transit constipation has been traditionally considered and classified as a functional disorder. However, clinical and manometric evidence has been accumulating that suggests how most of the motility alterations in STC might be considered of neuropathic type.In addition, further investigations showed that subtle alterations of the enteric nervous system, not evident to conventional histological examination, may be present in these patients. In the present article we will discuss these evidences, and will try to put them in relation with the abnormal motor function of the large bowel documented in this pathological condition.

THREE-DIMENSIONAL COMPUTED TOMOGRAPHY-GUIDED RADIOFREQUENCY TRIGEMINAL RHIZOTOMY FOR TREATMENT OF IDIOPATHIC TRIGEMINAL NEURALGIA

Objective To evaluate the effectiveness of three-dimensional computed tomography （3D-CT） guided radiofi＇equency trigeminal rhizotomy （RF-TR） in treatment of idiopathic trigeminal neuralgia （1TN）. Methods From 1999 to 2001, 18 patients with ITN were treated with percutaneous controlled RF-TR. Intraoperative 3D-CT scanning was performed to guide the trajectory of the puncture. After correction of the needle tip according to the CT scans and stimulation effects, 2 to 5 lesions were made for a duration of 60-90 seconds at a temperature of 60℃ to 75℃ depending on the pain distribution and the age of patient. The needles located in foramen ovale. Pain alleviated immediately with no serious complication in all patients. The patients were followed up for an average of 31.5 months （range 24-41 months）. Acute pain relief was experienced by 17 patients after the procedure, reaching an initial success rate of 94.4%. Early （〈 6 months） pain recurrence was observed in 2 patients （11.1%）, whereas late （〉 6 months） recurrence was reported in 3 patients （16.7%）. Thirteen patients had complete pain control, with no need for medication thereafter. Five cases experienced partial pain relief, but required medication at a lower dose than in the preoperative period. Conclusion 3D-CT foramen ovale locations can raise the successful rate of puncture, enhance the safety, and reduce the incidence rate of complication.

Effects of nuclei ambiguus and dorsal motor nuclei of vagus on gastric H^+ and HCO_3^- secretion in rats

AIM: To determine the effects of electrical stimulation of nucleus ambiguus (NA) and dorsal motor nuclei of vagus (DMV) on gastric acid and bicarbonate secretion in rats. METHODS: NA and DMV in rats were electrically stimulated. Pylorus ligation or esophagus perfusion was used to collect the gastric secretion. The titratable H+ quantum, H+ concentration, HCO3- secretion quantum were measured. RESULTS: Electrical stimulation of NA had no effects on the volume of gastric juice, titratable acidity and acid concentration, but elicited a pronounced increase in the total bicarbonate. However, electrical stimulation of DMV significantly increased the titratable acidity, the volume of gastric juice and the acid concentration. Similarly, electrical stimulation of either NA or DMV decreased the respiratory frequency and sinus bradycardia. CONCLUSION: NA in rats can not control the secretion of gastric acid but the secretion of bicarbonate in gastric juice, while DMV controls the secretion of gastric acid.

Is the pain in chronic pancreatitis of neuropathic origin? Support from EEG studies during experimental pain

AIM: To prove the hypothesis that patients with chronic pancreatitis would show increased theta activity during painful visceral stimulation. METHODS: Eight patients and 12 healthy controls underwent an experiment where the esophagus was electrically stimulated at the pain threshold using a nasal endoscope. The electroencephalogram (EEG) was recorded from 64 surface electrodes and "topographic matching pursuit" was used to extract the EEG information in the early brain activation after stimulation. RESULTS: A major difference between controls and patients were seen in delta and theta bands, whereas there were only minor differences in other frequency bands. In the theta band, the patients showed higher activity than controls persisting throughout the 450 ms of analysis with synchronous brain activation betweenthe channels. The main theta components oscillated with 4.4 Hz in the patients and 5.5 Hz in the controls. The energy in the delta (0.5-3.5 Hz) band was higher in the controls, whereas the patients only showed scattered activity in this band. CONCLUSION: The differences in the theta band indicate that neuropathic pain mechanisms are involved in chronic pancreatitis. This has important implications for the understanding and treatment of pain in these patients, which should be directed against drugs with effects on neuropathic pain disorders.

Liver transplantation for metastatic neuroendocrine tumor: A case report and review of the literature

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term ＂carcinoid＂. Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases, alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocin-based chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived. Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver. However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or Iocoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.

A case of an intussuscepted neuroendocrine carcinoma of the appendix

We have described a previously unreported entity of an intussuscepted neuroendocrine carcinoma of the appendix. Our patient was a 70-year-old man whose only complaint was insipient weight loss. Colonoscopy showed a malignant cecal ＂polyp＇; and an extended right hemicolectomy was performed. We have reviewed the literature on the causes of appendiceal intussusception and their appropriate treatment options, and clarified the classification of neuroendocrine tumors of the gastrointestinal tract.

Investigation of fundo-antral reflex in human beings

AIM： To examine the sensory and motor response（s） of the stomach following fundic distention and to assess whether cholinergic mechanisms influence these responses. METHODS： Fundic tone, gastric sensory responses and antral motility were evaluated in eight healthy volunteers after a probe with two sensors was placed in the antrum and a highly compliant balloon in the fundus. Isobaric balloon distentions were performed with a barostat. Study was repeated in six volunteers after intravenous atropine was given. RESULTS： Fundic antral contractions curve was higher First sensation distention induced large amplitude in all subjects. The area under the （P〈0.05） during fundic distention. was reported at 12±4 mmHg, moderate sensation at 18±4 mmHg and discomfort at 21±4 mmHg. Discomfort was associated with a decrease in antral motility. After atropine was given, the area under the curve of pressure waves and fundic tone decreased （P〈0.05）. Sensory thresholds were not affected. CONCLUSIONS： Fundic balloon distention induces an antral motor response, the fundo-antral reflex, which in part may be mediated by cholinergic mechanisms.

Gliomatosis Cerebri

Gliomatosis Cerebri （GC） is a rare tumor of the central nervous system. It is defined as a diffuse glial tumor that extensively infiltrates the brain, involving more than two lobes. And it is listed as a subtype of astrocytic tumors according to the newest 2007 （4th edition） WHO classification of tumors of the Central Nervous System. GC can be subdivided into Type I and Type II. Clinical findings for patients with GC are usually subtle and nonspecific. The lesions of GC generally show hypo, or isodensity on CT; a poorly defined diffuse hypoor isointense signal on Tl-weighted images, and a scattered diffuse hyperintense signal on T2-weighted images. Histological examination of GC reveals widespread infiltration of neoplastic glial cells with minimal destruction of pre-existing structures. Diagnosis of GC can be ascertained on the basis of a combination of clinical, radiological and pathological data. The treatment of GC includes radiotherapy and chemotherapy; however, the optimal therapeutic strategy is still not well established and prognosis of GC remains poor. This report reviews in detail the aspects of GC mentioned above, and three controversial issues are also discussed in the report.

AN UNUSUAL BILATERAL VAGAL PARAGANGLIOMAS: ONE CASE STUDY

VAGAL paraganglioma （VP） is an uncommon neoplasm originating from neural crest paraganglion cells located along the vagus nerve, repre-senting less than 5 % of all paragangliomas of the head and neck Despite improvement in microsurgical techniques,

Establishment of a mechanical injury model of rat hippocampal neurons in vitro

Objective: To establish a simple, reproducible, and practical mechanical injury model of hippocampal neurons of Sprague-Dawley rats in vitro. Methods: Hippocampal neurons isolated from 1-2-day old rats were cultured in vitro. Mild, moderate and severe mechanical injuries were delivered to the neurons by syringe needle tearing, respectively. The control neurons were treated identically with the exception of trauma. Cell damage was assessed by measuring the Propidium Iodide (PI) uptaking at different time points ( 0.5, 1, 6, 12 and 24 hours) after injury. The concentration of neuron specific enolase was also measured at some time points.Results: Pathological examination showed that degeneration, degradation and necrosis occurred in the injured cultured neurons. Compared with the control group, the ratio of PI-positive cells in the injured groups increased significantly after 30 minutes of injury (P< 0.05). More severe the damage was, more PI-positive neurons were detected. Compared with the control group, the concentration of neuron specific enolase in the injured culture increased significantly after 1 hour of injury (P< 0.05).Conclusions: The established model of hippocampal neuron injury in vitro can be repeated easily and can simulate the damage mechanism of traumatic brain injury, which can be used in the future research of traumatic brain injury.

Neurogenic pulmonary edema in head injuries: analysis of 5 cases

Objective: To review the pathophysiology and study the diagnosis and clinical management of neurogenic pulmonary edema (NPE). Methods: The data of 5 patients who developed NPE after head injury treated in our hospital form December 1995 to May 2003 were collected and analyzed. Results: The patients developed dyspnea and respiratory failure 2-8 hours after neurologic event. Four of the 5 patients presented with pink frothy sputum. Chest radiography showed bilateral diffuse infiltrations in all the 5 patients. After supportive measures such as oxygen support and pharmacologic therapy, 4 patients recovered in 72 hours and one patient died. Conclusions: The pathophysiologic mechanisms of NPE is unclear. In acute respiratory failure following head injury, NPE must be given much attention and timely and effective measures should be taken.