Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation.

BACKGROUND: Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS: Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS: Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS: Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.     

Randomized trial of olanzapine versus placebo in the symptomatic acute treatment of the schizophrenic prodrome.

BACKGROUND: The prodromal phase of schizophrenic disorders has been described prospectively. The present study aimed to determine the short-term efficacy and safety of olanzapine treatment of prodromal symptoms compared with placebo. METHODS: This was a double-blind, randomized, parallel-groups, placebo-controlled trial with fixed-flexible dosing conducted at four sites. Sixty patients met prodromal diagnostic criteria, including attenuated psychotic symptoms, as determined by structured interviews. Olanzapine 5-15 mg daily or placebo was prescribed for 8 weeks. RESULTS: In the mixed-effects, repeated-measures analysis, the treatment x time interaction for the change from baseline on the Scale of Prodromal Symptoms total score was statistically significant, and post hoc analyses revealed that the olanzapine-placebo difference reached p<.10 by week 6 and p<.05 at week 8. Ratings of extrapyramidal symptoms remained low in each group and were not significantly different. Olanzapine patients gained 9.9 lb versus.7 lb for placebo patients (p<.001). CONCLUSIONS: This short-term analysis suggests olanzapine is associated with significantly greater symptomatic improvement but significantly greater weight gain than is placebo in prodromal patients. Extrapyramidal symptoms with olanzapine were minimal and similar to those with placebo. Future research over the longer term with more patients will be needed before recommendations can be made regarding routine treatment.     

Antigenic characterization of endothelial cell-derived microparticles and their detection ex vivo

Summary. Background: Endothelial activation and dysfunction are associated with several diseases. However, hardly any specific markers are available. Microparticles (MP) from endothelial cells (EC; EMP) were reported in patient groups and healthy individuals. The antibodies used to detect EMP, however, were mainly directed against antigens without EC specificity. Objectives: We evaluated the antigens on EC and EMP to establish proper markers for EMP detection. Methods: EMP were isolated from supernatants of resting and interleukin (IL)‐1α activated human umbilical vein EC (HUVEC; n = 3; 0–72 h), stained with annexin V and monoclonal antibodies, and analyzed by flow cytometry. Human platelet‐MP (PMP), the main MP population in plasma, were prepared in vitro. EMP and PMP were studied in plasma from systemic lupus erythematosus (SLE) patients (n = 11) and healthy individuals (n = 10). Results: Platelet–endothelial cell adhesion molecule‐1 (PECAM‐1), α_ν and β₃ were constitutively exposed on HUVEC, but (almost) absent on EMP (<15% positive for α_ν and β₃), or only exposed on a subpopulation (PECAM‐1; 30–60%). Activated HUVEC (>80%) and (subpopulations of) EMP exposed E‐selectin and tissue factor. PMP strongly exposed PECAM‐1, β₃, and glycoprotein (GP)Ib (CD42b), but not α_ν or E‐selectin. GPIb and P‐selectin (CD62P) were absent on EMP. Plasma samples contained 0.5% MP staining for E‐selectin and/or α_ν. Plasma from one SLE patient contained E‐selectin exposing MP (21%), but little α_ν‐positive MP. Conclusions: EC release EMP in vitro. The antigenic phenotype of EMP released from resting and IL‐1α‐stimulated EC differs among each other as well as from resting and stimulated EC, respectively. E‐selectin exposed on IL‐1α‐stimulated EC is a valid marker for EMP detection ex vivo to establish endothelial cell activation.     

Frequency of immediate adverse effects associated with apheresis donation

BACKGROUND: Apheresis donation is considered safe, but the incidence of adverse effects has not been determined in a large multicenter series of donations with modern instruments. STUDY DESIGN AND METHODS: The Hemapheresis Committee of the American Association of Blood Banks devised a uniform questionnaire that asked about 32 specific adverse effects. Transient paresthesia and mild vasovagal events were excluded. A survey was conducted in 1995; 17 centers returned 19,611 responses concerning 250 to 2,000 consecutive apheresis donations per center. RESULTS: Six hundred adverse effects were reported in 428 donations (2.18% of donations). Pain or hematoma at a venipuncture site was the most common response (1.15% of donations); only 203 donations had other (nonvenipuncture) adverse effects (1.04%). Total and nonvenipuncture rates were, respectively, 4.84 and 2.92 percent for 2,295 first donations and 1.78 and 0.77 percent for 17,303 repeat donations (p < 0.001). Rates of nonvenipuncture symptoms in first and repeat donations were, respectively, citrate-induced nausea and/or vomiting, 0.87 and 0.27 percent; tetany, 0.09 and 0.04 percent; pallor and/or diaphoresis, 1.87 and 0.32 percent; vasovagal nausea and/or vomiting, 0.87 and 0.13 percent; syncope and/or seizure, 0.39 and 0.04 percent; and chills and/or rigors, 0.31 and 0.01 percent. The overall rate of donor unconsciousness was 0.08 percent. Hemolysis was reported twice. Clotting or leakage occurred in 0.08 percent of donations, and inability to return blood occurred in 0.16 percent. No life-threatening adverse effects were reported. Procedure-specific nonvenipuncture rates were 1.05 percent of 17,584 platelet donations, 0.67 percent of 594 white cell donations, and 0.37 percent of 1,354 plasma donations. Center-specific rates varied from 0.32 to 6.81 percent of donations for total adverse effects and from 0.11 to 2.92 percent of donations for nonvenipuncture events. CONCLUSION: Apheresis donation is a safe undertaking, suitable for voluntary blood donors, with a very low risk of serious adverse effects. The risk of unconsciousness is lower than that found in many studies of whole-blood donation.     

COR TRIATRIATUM: UNUSUAL CAUSE OF TRANSIENT ISCHAEMIC ATTACKS IN A 67-YEAR-OLD MAN

SUMMARY Cor triatriatum is a rare congenital cardiac malformation, and in its most common form is characterised by a membrane that separates the left atrium into a proximal and distal chamber. First manifestation in adulthood has been reported previously, but at 67 years of age this patient is one of the oldest to present for the first time. It was diagnosed after a probable TIA, episodic vertigo and central retinal artery occlusion. The value of echocardiography in patients with neurological disease of presumed embolic origin is demonstrated here.     

绿色荧光蛋白转基因干细胞在癫痫大鼠脑内的存活及对脑电的影响

目的:观察神经干细胞和骨髓基质干细胞移植至癫痫大鼠海马后的存活、迁移与周围组织的整合、修复和对癫痫大鼠脑电的影响。方法:实验于2005-03/2006-02在昆明医学院神经科学研究所完成。①实验材料:6～8周龄绿色荧光蛋白转基因小鼠,雌雄不限,体质量40～60g,由新加坡国立大学提供。健康雄性SD大鼠88只,体质量(300±20)g,由昆明医学院动物科提供。将88只SD大鼠随机分为对照组(n=8)、癫痫未移植组(n=8)、生理盐水组(n=24)、神经干细胞移植组(n=24)、骨髓基质干细胞移植组(n=24)。②实验方法:剖取绿色荧光蛋白小鼠孕鼠脑,分离获得整个海马进行神经干细胞的分离,并采用免疫化学方法鉴定。取绿色荧光蛋白转基因小鼠股骨,进行骨髓基质干细胞的分离,并采用免疫组织化学方法鉴定。癫痫未移植组、生理盐水组、神经干细胞移植组、骨髓基质干细胞移植组大鼠注射300×105U/kg,浓度80万U/mL青霉素制作癫痫大鼠模型,连续注射7d,每次癫痫发作按Racine评分标准评分,对照组大鼠腹腔注射相同剂量的生理盐水作为对照。将分离、培养绿色荧光蛋白转基因小鼠神经干细胞和骨髓基质干细胞,移植至青霉素致癫痫大鼠的右侧海马内。③实验评估:移植后1,2,4周观察移植干细胞在大鼠脑内存活和迁移情况,并检测大鼠脑电改变。结果:88只大鼠全部进入结果分析,中途无脱落。①大鼠行为学改变:癫痫未移植组、生理盐水组、神经干细胞移植组、骨髓基质干细胞移植组大鼠均达到Racine分级Ⅳ～Ⅴ级,癫痫模型制备成功。②各组大鼠的脑电改变:移植干细胞可减少癫痫大鼠脑电的痫性发放,降低癫痫波的波幅,具有明显的抗痫效应。③干细胞移植后在海马内的存活和迁移:移植神经干细胞可在青霉素致痫鼠脑内存活和迁移,但随时间的延长,存活细胞数目减少。结论:干细胞移植于青霉素诱发的癫痫大鼠脑内能够存活、迁移,能够改善癫痫鼠的脑电生理功能,提示干细胞移植可能成为一种有效的癫痫治疗手段。     

Rapid freezing of whole blood or buffy coat samples for polymerase chain reaction and cell culture analysis: application to detection of human immunodeficiency virus in blood donor and recipient repositories. The Transfusion Safety Study Group

Storage of lymphocytes for later use in prospective epidemiologic studies of blood donors and transfusion recipients has been limited by the cost of separating peripheral blood mononuclear cells (PBMCs). When the Transfusion Safety Study began in 1985, it was decided to establish a cell repository of cryopreserved buffy coat (BC) samples, and thus far over 20,000 samples have been accumulated from enrolled subjects. To determine if these specimens could be used for polymerase chain reaction, a simple thawing and pelleting technique for recovering hemoglobin-free total white cells (WBCs) was developed. To validate the technique, parallel analysis was conducted of BCs, whole blood (WB), and PBMC samples from human immunodeficiency virus type 1 (HIV-1)- seropositive subjects. Immediate postthaw cell courts of 29 frozen- thawed (F-T) WB and BC samples averaged 90 percent of the prefreeze (input) values. Representative WBC populations were obtained by immediate pelleting. Amplification of HIV-1 gag sequences from F-T BCs and F-T WB was 94 and 75 percent, respectively, which is as sensitive as that obtained with freshly separated PBMC lysates. Quantitative HIV- 1 proviral load analysis by serial dilution of 23 F-T BCs and 8 WB lysates showed results comparable to those obtained with lysates of fresh PBMCs. Values for WBC differential and immunophenotyping could be applied to express viral load relative to total WBCs, PBMCs, or CD4+ cells. These results establish the basis for simplified virologic analysis of cryopreserved BC or WB specimens.     

Neutrophil transfusions: kinetics and functions of neutrophils mobilized with granulocyte-colony-stimulating factor and dexamethasone

BACKGROUND: The collection of adequate numbers of neutrophils (polymorphonuclear leukocytes, PMNs) from normal donors has long hampered the development of neutrophil transfusion therapy. The stimulation of donors with granulocyte-colony-stimulating factor (G- CSF) plus dexamethasone is a promising way of improving PMN collections. STUDY DESIGN AND METHODS: Sixteen normal subjects received G-CSF (600 micrograms subcutaneously) and dexamethasone (8 mg by mouth) 12 hours before leukapheresis. Measurements included PMN morphology, immunophenotype analysis, chemiluminescence, bactericidal activity, in vivo kinetics, and adverse effects. RESULTS: A mean of 77.4 +/− 6.4 × 10(9) PMNs was collected with each leukapheresis; 14 percent were bands. PMNs had increased surface expression of CD11b, CD18, CD14, CD32, and CD64. Bactericidal capacity against Staphylococcus aureus was normal. Inducible respiratory burst was maintained, although the responses to some agonists were diminished. Returned leukapheresis cells labeled with 3H-diisopropylfluorophosphate had a modestly decreased percentage of recovery and circulated with a prolonged half- life. Migration of these cells to skin chambers was approximately equal to that of the subjects' own blood PMNs. Adverse effects included transient bone pain, headache, hunger, and insomnia. CONCLUSIONS: Precollection treatment of leukapheresis donors with G-CSF plus dexamethasone is an effective way to enhance the collection of PMNs with normal or near-normal functional properties for PMN transfusion therapy.     

A comparative trial of granulocyte-colony-stimulating factor and dexamethasone, separately and in combination, for the mobilization of neutrophils in the peripheral blood of normal volunteers

BACKGROUND: The clinical utility of polymorphonuclear neutrophil (PMN) transfusion therapy has been compromised, in part, by the inability to obtain sufficient quantities of functional neutrophils from donors. To define the optimal conditions for mobilization of PMNs in granulocyte donors, the effects of granulocyte-colony-stimulating factor (G-CSF) and dexamethasone, separately and in combination, on PMN counts in normal volunteers were compared. STUDY DESIGN AND METHODS: Five normal subjects were randomly assigned to each of the following single-dose regimens in 5 consecutive weeks: 1) G-CSF, 300 micrograms given subcutaneously; 2) G-CSF, 600 micrograms subcutaneously: 3) dexamethasone, 8 mg given orally; 4) G-CSF, 300 micrograms subcutaneously, plus dexamethasone, 8 mg orally; and 5) G-CSF, 600 micrograms subcutaneously, plus dexamethasone 8 mg orally. Venous blood was collected at 0, 6, 12, and 24 hours after drug administration for the determination of absolute neutrophil counts (ANCs). RESULTS: Maximal ANC was achieved at 12 hours after each regimen, except dexamethasone alone (maximum, 24 hours). Dexamethasone significantly increased the maximal ANC induced by either dose of G-CSF alone (p < 0.05). The greatest mobilization of PMNs occurred after the administration of G-CSF (600 micrograms) and dexamethasone (8 mg); the ANC increased from a mean baseline value of 3,594 per microL to 43,017 per microL at 12 hours. All of the drug regimens were well tolerated. CONCLUSION: Dexamethasone significantly increases the level of neutrophilia induced in normal subjects by G-CSF. The combination of dexamethasone and G-CSF (at the dosages used in this study) is a convenient, well-tolerated regimen for the mobilization of PMNs in the peripheral blood of granulocyte donors. Moreover, the optimal quantitative yield of PMNs is likely to be achieved by leukapheresis 12 hours after drug administration.