DOPAMINERGIC PROJECTION TO THE CENTRAL AMYGDALA MEDIATES THE FACILITATORY EFFECT OF CCK-8US AND CAERULEIN ON MEMORY IN RATS

The involvement of dopaminergic projection to the central amygdala in the facilitatory effect of cholecystokinin unsulphated octapeptide (CCK-8US) and caerulein (CER) on memory motivated affectively was investigated in male rats. CCK-8US and CER were administered subcutaneously at the doses of 10 micrograms kg-1and 0.5 microgram kg-1, respectively, immediately after a single learning trial in a passive avoidance situation, after bilateral 6-OHDA lesions to the central amygdala. Bilateral 6-OHDA lesions to the central amygdala totally abolished the facilitatory effect of CCK-8US and CER on retention of passive avoidance behaviour evaluated 24 h after the learning trial. These results may indicate that the facilitatory effect of CCK-8US and CER on memory motivated affectively is mediated by dopaminergic projection from ventral tegmental area to the central amygdala.     

Marrow harvesting from normal donors

The experience at a single institution in harvesting marrow for allogeneic transplantation on 1,270 occasions from 1,160 normal donors is presented in detail, together with an analysis of all the donor complications. Four donors were less than 2 years old, and the youngest was 6 1/2 months. No special difficulties were encountered with these young donors. Hospitalization time was three days or less for 99% of the procedures. Six donors had life-threatening complications; three of a cardiopulmonary and two of an infectious nature, and one cerebrovascular embolic episode. Significant operative site morbidity, usually transient neuropathies, occurred in ten procedures. Ten percent of the donations were associated with transient postoperative fever of unknown origin. Increasing donor age was associated with a reduction of the cellularity of the marrow harvest. The use of stored autologous blood permitted the avoidance of blood bank transfusion in 81% of males, 69% of females, and 50% of children. It was concluded that the procedure was associated with a very low risk of complication, but that the involvement of normal donors in such an operation justifies stringent monitoring.     

Allogeneic marrow transplantation for refractory anemia: a comparison of two preparative regimens and analysis of prognostic factors

From 1990 to 1993 we performed a prospective study of busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) in 30 patients with refractory anemia (RA) undergoing related (n = 17) or unrelated (n = 13) donor marrow transplantation. Nineteen patients survive disease free (63% 3- year actuarial disease-free survival [DFS]) and no patient relapsed. These results were compared to those of 38 historical controls with RA treated with cyclophosphamide and total body irradiation, of whom 22 are disease-free survivors and 1 relapsed. After correcting for significant variables between the two treatment groups, we found no statistically significant difference in outcome based on preparative regimen. Combining data from these 68 patients plus 2 additional patients with RA treated before 1993 with busulfan and cyclophosphamide, we identified four variables independently associated with improved survival: younger age, shorter disease duration, lower neutrophil count pretransplant, and lower hematocrit pretransplant. We also found that 15 patients 40 to 55 years of age had a 46% 3-year actuarial DFS and 26 patients receiving unrelated or mismatched related donor marrow had a 50% 3-year actuarial DFS. We conclude that there does not appear to be any significant difference in outcome based on preparative regimen in this patient population. In addition, allogeneic bone marrow transplantation may be a reasonable approach to therapy of RA early after diagnosis. However, whether early intervention with transplantation prolongs survival over that expected without transplantation cannot be ascertained with certainty from available data.     

Importance of Tachycardia Cycle Length for Differentiating Typical Atrial Flutter from Scar‐Related in Adult Congenital Heart Disease

Background: Radiofrequency catheter ablation (RFCA) for intraatrial reentrant tachycardia (IART) in congenital heart disease (CHD) remains difficult. Methods: Thirty‐four consecutive adult patients (age, 37.6 ± 12.8 years; male, 21) with previously repaired CHD and IART underwent an electrophysiological study and RFCA. CHD included atrial septal defect (ASD, n = 14), tetralogy of Fallot (n = 11), ventricular septal defect (n = 4), pulmonary atresia (n = 2), atrioventricular septal defect (n = 1), transposition of the great arteries (n = 1), and double‐outlet right ventricle (n = 1). Results: Duration of CHD repair to IART onset was 19.1 ± 8.5 years. Thirty and four patients had single‐ and double‐loop reentrant tachycardia, respectively. Among the total of 38 IARTs, which were mapped, 22 (57.9%) and 13 (34.2%) IARTs were cavotricuspid isthmus (CTI)‐dependent atrial flutter (AFL) and scar‐related AFL, respectively. Typical AFL electrocardiography findings including definite sawtooth appearance in inferior leads and positive F wave in lead V1 were observed in only 12 of 21 patients (57.1%) with CTI‐dependent AFL. CTI‐dependent AFL had a significantly longer tachycardia cycle length (TCL) than scar‐related AFL (267.6 ± 34.4 ms and 235.9 ± 37.0 ms, respectively; P = 0.031). TCL > 250 ms had 79% sensitivity as the cutoff value for differentiating CTI‐dependent from scar‐related AFL. The acute success rates of RFCA in CTI‐dependent and scar‐related AFLs were 85.7% and 90.0%, respectively. The recurrence rates in CTI‐dependent and scar‐related AFLs were 11.1% and 11.1%, respectively, during a follow‐up of 21.2 ± 28.3 months. Conclusions: CTI‐dependent AFL was the most common IART in adult patients with repaired CHD and was easily manageable by RFCA. TCL might help to differentiate CTI‐dependent AFL from other IARTs. (PACE 2012;35:1338–1347)     

The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis [see comments]

The effects of daily administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to eight normal volunteers donating granulocytes for neutropenic relatives undergoing marrow transplantation were studied. Granulocyte donors consisted of seven marrow donors (5 syngeneic, 2 HLA identical) and one haploidentical son who had not donated marrow. All donors were administered daily rhG-CSF at a mean dose of 5 micrograms/kg/d (range 3.5 to 6.0) for a mean of 11.75 days (range 9 to 14 days), and granulocytes were collected a mean of 7.6 times (range 4 to 12). RhG-CSF was well tolerated and only minor side effects were observed. All donors became anemic from marrow donation and the removal of red blood cells during the collection procedures. Red blood cell transfusions were not given. All donors had a decrease in platelet counts and the magnitude of the decrement appeared to be greater than in historical donors. This was due in part to increased removal of platelets with the collection product, but a direct effect of rhG-CSF on platelet production cannot be excluded. The mean precollection granulocyte level was 29.6 x 10(9)/L (range 11.8 to 79.8), which was a 10-fold increase over baseline. The mean number of granulocytes collected was 41.6 x 10(9) (range 1.3 to 144.1), which was a six-fold increase over historical donors not receiving rhG-CSF. The mean granulocyte level 24 hours after transfusion into neutropenic recipients was 0.95 x 10(9)/L (median 0.57 and range .06 to 9.47). This study indicates that rhG-CSF is safe to administer to normal individuals, significantly improves the quantity of granulocytes collected, and results in significant circulating levels of granulocytes in neutropenic recipients. Further studies to evaluate rhG- CSF in normal granulocyte donors are warranted.     

Allogeneic bone marrow transplantation for 93 patients with myelodysplastic syndrome

We treated 93 patients with myelodysplastic syndrome using cyclophosphamide and either total body irradiation (n = 88) or busulfan (n = 5) followed by marrow transplantation. Sixty-five marrow donors were genotypically HLA-identical siblings and 28 were other family members or unrelated donors. Before transplantation all patients had either severe neutropenia or thrombocytopenia or had greater than 5% blasts in the marrow or peripheral blood. The probabilities of disease- free survival, relapse, and non-relapse mortality at 4 years were 41%, 28%, and 43%, respectively. Multivariate analysis revealed that younger age and shorter disease duration were significantly associated with improved disease-free survival and decreased non-relapse mortality. Relapse was seen only in patients with excess blasts at the time of transplantation (51% at 4 years). Patients younger than age 40 and without excess blasts had a 4-year disease-free survival of 62%. This study confirms that allogeneic marrow transplantation can cure some patients with myelodysplasia. Because of the favorable outcome in younger patients without excess blasts, we recommend that transplantation be considered early for patients younger than age 40, before disease progression or development of life-threatening cytopenias. For older patients and those with excess blasts, changes in the transplant procedure will be necessary to improve outcome.     

冠状动脉痉挛诱发心律失常的临床特点及治疗效果

目的探讨冠状动脉痉挛（CAS）诱发心律失常的临床特点及治疗效果。方法选择1998年7月至2008年12月期间入住本院的16例CAS患者,CAS的诊断根据病史和症状,结合标准12导联心电图、动态心电图及冠状动脉造影等检查确定。结果16例患者CAS发作时伴有心绞痛和心电图ST段抬高。全部病例均合并缓慢性和／或快速性心律失常,其中缓慢性心律失常6例,二、三度房室阻滞5例,窦性静止1例;快速性心律失常12例,其中持续性室性心动过速（室速）和心室颤动（室颤）5例,非持续性室速5例,室性早搏2例。冠状动脉造影显示,4例冠状动脉完全正常,4例冠状动脉狭窄等于或超过50％,其余8例冠状动脉狭窄均≤45％。全部病例均接受了大剂量钙拮抗剂和硝酸酯类的联合抗血管痉挛治疗。冠状动脉有明显狭窄的4例患者接受了介入治疗。除1例患者死亡外,其余患者平均随访（52．3±18．9）个月,无心绞痛及晕厥发作。结论有或无冠状动脉病变的CAS均可诱发缓慢性和／或快速性室性心律失常;除针对冠状动脉基础病变治疗外,地尔硫革和硝酸酯类等联合抗痉挛治疗是主要的治疗措施。     

Peripheral blood stem cell donation: an analysis from the International Bone Marrow Transplant Registry (IBMTR) and European Group for Blood and Marrow Transplant (EBMT) databases

Donation-related data for 1488 allogeneic peripheral blood stem cell (PBSC) transplants reported to the International Bone Marrow Transplant Registry (IBMTR) or the European Blood and Marrow Transplant Group (EBMT) by 152 teams worldwide between 1994 and 1998 were reviewed. In 1998, 26% of allografts registered with the IBMTR were collected from blood. Median age of PBSC donors was 38 years (range <1-76), and 55% were male. Of 1486 donor-recipient pairs evaluable for HLA compatibility, 1322 (89%) were HLA-identical siblings. Recombinant human granulocyte colony-stimulating factor (G-CSF) was employed to mobilize PBSCs in almost all (99%) cases. One hundred and seventy (20%) of 828 evaluable PBSC donors had a central catheter placed for leukapheresis. Eighty-five percent of 1321 evaluable PBSC grafts were collected with one or two leukaphereses. There were 15 reported donation-related adverse events (1% of evaluable donors). Complications were catheter-related in five. No donation-related fatalities were reported. These data suggest that PBSC donation is becoming more prevalent worldwide. It appears to have a safety profile comparable to marrow harvesting, although experience with the latter is much more extensive.     

Allogeneic marrow transplantation for multiple myeloma: an analysis of risk factors on outcome

Between September 1987 and December 1994, 80 patients with multiple myeloma (MM) received high-dose busulfan and cyclophosphamide without (n = 57) or with modified total body irradiation (n = 23) followed by marrow from allogeneic donors. At transplant, 71% of the patients had disease that was refractory to chemotherapy. Thirty-five patients died of transplant-related causes within 100 days and 11 deaths occurred later. The actuarial probabilities of survival and progression-free survival were .24 +/- 0.17 and .20 +/- 0.10 at 4.5 years. Complete remissions were obtained in 36% of patients who had actuarial probabilities of survival and event-free survival of .50 +/- 0.21 and .43 +/- 0.17 at 4.5 years. In a multivariate analysis, adverse risk factors for outcome endpoints included: transplantation greater than 1 year from diagnosis; beta-2 microglobulin > 2.5 at transplant; female patients transplanted from male donors; patients who had received greater than eight cycles of chemotherapy before transplant and Durie stage 3 disease at the time of transplant. These results indicate that allografting for patients with MM can result in long-term disease-free survival for a minority of patients. Efforts to reduce transplant- related mortality should focus on earlier transplantation, less toxic treatment regimens, better supportive care, and improved prevention and treatment of graft-versus-host disease (GVHD).