补阳还五汤对脑缺血再灌注后星形胶质细胞及热休克蛋白的影响

目的探讨补阳还五汤对脑缺血再灌注后星形胶质细胞(AS)及热休克蛋白(HSP70)的影响.方法采用沙土鼠双侧颈动脉夹闭脑缺血模型,于脑缺血15min再灌注24 h和48 h后,运用免疫组化技术观察星形胶质纤维酸性蛋白(GFAP)及热休克蛋白70的蛋白基因表达.结果缺血再灌注24 h后,GFAP免疫阳性反应达高峰,补阳还五汤可使GFAP免疫反应减轻;缺血再灌注48 h后GFAP表达减弱,补阳还五汤可使其增强;缺血再灌注后48 h,HSP70 mRNA及蛋白表达明显增强,补阳还五汤可明显抑制其转录外,还可轻度降低HSP70的翻译.结论补阳还五汤对脑缺血损伤后神经功能的保护作用可能与调节星形胶质细胞及抑制缺血脑损伤HSP70基因的过度表达作用有关.     

Surgical treatment of pulmonary recurrence after hepatectomy for colorectal liver metastases

BACKGROUND/AIMS: Although pulmonary recurrence is frequent among the extrahepatic recurrences after hepatectomy, the efficacy of surgical treatment for pulmonary recurrence after hepatectomy has not been confirmed. Surgical resection of pulmonary recurrence after hepatectomy for colorectal metastases was reviewed retrospectively to evaluate the survival benefit. METHODOLOGY: From 1990 to 1995, 10 of the 17 patients with pulmonary recurrence after hepatectomy for colorectal metastases underwent surgical treatment. Ten patients underwent resection of pulmonary recurrence. RESULTS: Operative mortality was 0%, and a postoperative complication was observed in 1 patient after pulmonary metastasectomy. The overall 5-year survival rate after pulmonary metastasectomy was 10.0%, and the median survival was 21.7 (range: 2.4-77.9) months. One patient underwent resection two times for remnant lung recurrence after first lung metastasectomy, and is alive with no evidence of recurrence 77.9 months after the first pulmonary resection, and 50.7 months after the third pulmonary resection. In 3 patients with well-differentiated adenocarcinoma, the median survival time was 6.2 months (range: 2.4-9.7). The other hands, 7 patients with moderately differentiated adenocarcinoma have a longer median survival time of 29.2 months (range: 16.0-77.9). CONCLUSIONS: Pulmonary metastasectomy after hepatectomy for metastases from colorectal cancer is a safe treatment, and might offer prolonged survival for highly selected patients.     

Symptomatic bronchoconstriction after short-term inhalation of sulfur dioxide

We studied the relationship between duration and concentration of exposure in SO2-induced bronchoconstriction in 8 asthmatic subjects. On separate days, we administered SO2 in humidified air through a mouthpiece at 2 concentrations (0.5 and 1.0 ppm) for 3 time periods (1, 3, and 5 min) during eucapnic hyperpnea (60 L/min). Humidified air was administered for 5 min as a control. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw). The magnitude of the bronchoconstrictor response to both concentrations of SO2 increased progressively over the 3 time periods studied. The mean (+/- SE) increase in SRaw (in L x cm H2O/L/s) and percent increase above baseline (in parentheses) after each exposure to SO2 were as follows: 2.5 +/- 0.3 (34%) after 0.5 ppm for 1 min; 7.5 +/- 4.7 (93%) after 1.0 ppm for 1 min; 13 +/- 3.2 (173%) after 0.5 ppm for 3 min; 31.4 +/- 7.4 (395%) after 1.0 ppm for 3 min; 19.6 +/- 4.0 (234%) after 0.5 ppm for 5 min; 44.1 +/- 9.8 (580%) after 1.0 ppm for 5 min; 3.5 +/- 1.5 (46%) after humidified air for 5 min. For the group, the increases in SRaw caused by inhalation of both concentrations of SO2 for 1 min were small. However, 2 of 8 subjects did develop large increases in SRaw and chest tightness after inhalation of 1.0 ppm for 1 min. Seven of 8 subjects developed wheezing, chest tightness, or dyspnea and used an inhaled bronchodilator after inhalation of 0.5 ppm for 3 and 5 min and 1.0 ppm for 3 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)     

The Effects of Ventricular Fibrillation Duration and a Preceding Unsuccessful Shock on the Probability of Defibrillation Success Using Biphasic Waveforms in Pigs

Influence of VF Duration on Defibrillation Efficacy. introduction: While the defibrillation threshold has been reported to increase with ventricular fibrillation (VF) duration for monophasic waveforms, the effect of VF duration for biphasic waveforms is unknown. Methods and Results: The ED 50 requirements (the 50% probability of defibrillation success) for an endocardial lead system, which included a subcutaneous array, were determined by logistic regression using a recursive up-down algorithm for a biphasic waveform ((6/6 msec). The study was performed in two parts, each with eight pigs. In part 1, ED 50 was compared for shocks delivered after 10 seconds of VF and for shocks delivered after 20 seconds of VF following a failed first shock at 10 seconds. Energy at ED 50 decreased from 6.5 ± 0.9, J for shocks delivered after 10 seconds of VF to 4.9 ± 0.8, J (P < 0.01) for shocks delivered after 20 seconds. To determine if improved second shock efficacy was a result of preconditioning by the failed first shock or a function of VF duration, part 2 of the study compared defibrillation efficacy between shocks delivered after 10 seconds of VF with shocks delivered after 20 seconds of VF with and without a failed first shock at 10 seconds. Mean energy at ED 50 decreased from 10.1 ± 2.4, J for shocks delivered after 10 seconds of VF to 7.9 ± 2.4 J (P < 0.01) and 7.5 ± 3.2 J (P < 0.01) for shocks delivered after 20 seconds of VF with and without a failed first shock, respectively. The mean energy at KD 50 for shocks delivered after 20 seconds of VK with and without a failed first shock was not significantly different (P = 0.53). A strong linear correlation for energy at ED 50 was found between shocks delivered after 10 seconds of VF and shocks delivered after 20 seconds of VF following a failed first shock (r = 0.95, P < 0.01). Conclusion: (1) As opposed to monophasic shocks, ED 50 is significantly lower for biphasic shocks delivered after 20 seconds of VF compared with shocks delivered after 10 seconds of VF in pigs. (2) An unsuccessful biphasic shock in pigs does not affect the defibrillation efficacy for a subsequent shock. (3) ED 50 for a biphasic shock delivered after 20 seconds of VK is linearly related to ED 50 for a shock delivered after 10 seconds of VK.     

86例急性冠脉综合征患者他汀类药物治疗对肝功能的影响病例分析

摘 要 目的：探讨他汀类药物治疗急性冠脉综合征对肝功能的影响及安全性。方法：收集2014年2月至2014年7月于我院心内科住院治疗的86例急性冠脉综合征患者病例资料,入院即刻给予常规剂量他汀类药物治疗,检测24h内、7天、15天的肝脏转氨酶,根据服用他汀类药物后7天后肝功能(丙氨酸氨基转移酶)正常与否分成两组:肝功能正常组与肝功能异常组;分析两组肝脏转氨酶变化趋势。结果：两组入院后7天、15天无肝脏转氨酶超过正常高限3倍以上的病例;两组肝脏天门冬氨酸氨基转移酶（AST）入院24小时内均数明显增高,入院后7天、15天降至正常范围内;肝功能异常组入院24小时内丙氨酸氨基转移酶(ALT)均数呈轻中度增高,入院后7天、15天呈轻度增高;肝功能正常组入院24小时内丙氨酸氨基转移酶(ALT)均数呈轻中度增高,入院后7天、15天降至正常;结论：部分患者服用他汀类药物后肝功能ALT轻度增高,AST降至正常范围,急性冠脉综合征患者服用常规剂量他汀是安全的。     

Preoperative,intraoperative and postoperative risk factors for anastomotic leakage after laparoscopic low anterior resection with double stapling technique anastomosis

Anastomotic leakage(AL) is one of the most devastating complications after rectal cancer surgery. The double stapling technique has greatly facilitated intestinal reconstruction especially for anastomosis after low anterior resection(LAR). Risk factor analyses for AL after open LAR have been widely reported. However, a few studies have analyzed the risk factors for AL after laparoscopic LAR. Laparoscopic rectal surgery provides an excellent operative field in a narrow pelvic space, and enables total mesorectal excision surgery and preservation of the autonomic nervous system with greater precision. However, rectal transection using a laparoscopic linear stapler is relatively difficult compared with open surgery because of the width and limited performance of the linear stapler. Moreover, laparoscopic LAR exhibits a different postoperative course compared with open LAR, which suggests that the risk factors for AL after laparoscopic LAR may also differ from those after open LAR. In this review, we will discuss the risk factors for AL after laparoscopic LAR.     

Intestinal morphological changes during oral refeeding in a patient previously treated with total parenteral nutrition for small bowel resection

This report describes a patient who, after a subtotal resection of small intestine for an embolic obstruction of the superior mesenteric artery, was maintained on total parenteral nutrition for 30 days and then refed. Cytoproliferativc analysis of the intestinal mucosa, evaluated by peroral biopsies performed on days I, 5, 14 and 30 after oral refeeding, demonstrated an increase in ceil proliferation from 1 to 14 days after refeeding. followed by a return to starting values after 30 days. On days 1 and 5, we saw an intestinal hypoplasia that became a hyperplasia after 14 days of oral refeeding. Our data confirm the importance of oral nutrition for the small intestinal response after resection.     

Surgical management of recurrence after resection of colorectal liver metastases

The optimal treatment for recurrent lesions after hepatectomy for colorectal liver metastases is controversial. We report the outcome of aggressive surgery for recurrent disease after the initial hepatectomy and the influence on quality of life of such treatment. Forty-five (70%) of the 64 surviving patients developed recurrence after the initial hepatectomy for liver metastases. The determinants of hepatic recurrence were the distribution and the number of liver metastases. Twenty-eight (62%) of patients with recurrence underwent resection. A second hepatectomy was performed in 20 patients, and a third hepatectomy was done in 5 patients. Ten patients with pulmonary metastasis underwent partial lung resection on 14 occasions, while resection of brain metastases was performed in 3 patients on 5 occasions. There were no operative deaths after resection of recurrent disease. The morbidity rate was 28% after repeat hepatectomy, 21% after pulmonary resection, and 0% after resection of brain metastasis. The Karnofsky performance status (PS) after the last surgery was not significantly different from that after the initial hepatectomy. The 3- and 5-year survival rates after the second hepatectomy were 54% and 14%, respectively. The 3-and 5-year survival rates of the patients undergoing resection of extrahepatic recurrence were both 17%. The survival rate after resection of recurrent disease (n=28) was significantly better than that of patients (n=17) with unresectable recurrence (P < 0.05). For the 66 patients with colorectal liver metastases, the 5-year survival rate after initial hepatectomy was 50%. The distribution and the number of liver metastases and the presence of extrahepatic disease, as single factors, significantly affected prognosis after the initial hepatectomy. Multivariate analysis revealed that only the presence of extrahepatic metastasis and a disease-free interval of less than 6 months were independent predictors of survival after the initial and second hepatectomy, respectively. It is concluded that aggressive surgery is an effective strategy for selected patients with recurrence after initial hepatectomy. Careful selection of candidates for repeat surgery will yield increased clinical benefit, including long-term survival.     

Echocardiography of hypoplastic left heart syndrome

Echocardiography is critical in the assessment of patients with hypoplastic left heart syndrome. Fundamental techniques and standardised approaches are useful when evaluating patients with hypoplastic left heart syndrome prenatally, after birth, and before the Norwood operation (Stage 1); after the Norwood operation, before and after the superior cavopulmonary anastomosis (Stage 2); before and after the Fontan operation (Stage 3); and for chronic surveillance after the Fontan operation. From foetal assessment to ongoing surveillance after the Fontan procedure, echocardiography remains the primary technique for cardiac monitoring in this growing population of children and adults.     

Delayed conversion to sinus rhythm after direct-current countershock.

Elective cardioversion for supraventricular arrhythmias has been performed in 203 patients during a 30-month period beginning in May, 1972. In five instances conversion to normal sinus rhythm occurred well after the electric shock had been delivered. The interval ranged from 4 to 105 seconds after DC countershock. In one patient, atrial fibrillation clearly persisted for eight seconds after DC countershock, however, immediately after countershock the ventricular rate became regular and, in addition to the fibrillatory activity, apparent sinus P-waves became visible and the same regular rate persisted after disappearance of fibrillatory waves. This raised the possibility of atrial dissociation. Our experience suggests that if apparent failure of conversion is noted after DC countershock, a repeat shock at a higher level should not be administered immediately but only after observing the rhythm for up to two minutes. Other possible mechanisms of delayed conversion are discussed.     

False-positive Findings for Tumor Markers after Curative Gastrectomy for Gastric Cancer

The objective of this study was to assess the frequency and characteristics of false-positive results for tumor markers after curative gastrectomy for gastric cancer. Carcinoembryonic antigen and/or carbohydrate antigen 19-9 were periodically assessed for 168 patients who underwent curative gastrectomy. Cancer recurrence was observed for 17 (10.1%) patients and 151 (89.9%) were disease-free during the mean follow-up period of 23.1 months after the operation. The frequency of false-positive findings for tumor markers after gastrectomy was 14.3% (24/168) for all followed-up patients. Three different patterns of marker elevation were observed in the false-positive group. A false-positive finding for these markers was observed for patients with early-stage cancer and for those with chronic benign diseases, for example bronchitis, liver dysfunction, diabetes mellitus, and renal dysfunction. For most patients with false-positive findings for a marker a spontaneous decrease in the tumor marker was observed 1–2 months after the marker was first observed at a high level after the operation. Surgeons and oncologists should therefore keep in mind the high frequency of false-positive findings for tumor markers after curative gastrectomy for gastric cancer.     

Risk factors for bleeding after endoscopic mucosal resection

AIM: To clarify the risk factors for bleeding after endoscopic mucosal resection (EMR). METHODS: A total of 297 consecutive patients who underwent EMR were enrolled. Some of the patients had multiple lesions. Bleeding requiring endoscopic treatment was defined as bleeding after EMR. Odds ratios (OR) with 95% confidence intervals (CI), calculated by logistic regression with multivariate adjustments for covariates, were the measures of association. RESULTS: Of the 297 patients, 57 (19.2%) patients with bleeding after EMR were confirmed. With multivariate adjustment, the cutting method of EMR, diameter, and endoscopic pattern of the tumor were associated with the risk of bleeding after EMR. The multivariate-adjusted OR for bleeding after EMR using endoscopic aspiration mucosectomy was 3.07 (95%CI, 1.59-5.92) compared with strip biopsy. The multiple-adjusted OR for bleeding after EMR for the highest quartile (16-50 mm) of tumor diameter was 5.63 (95%CI, 1.84-17.23) compared with that for the lowest (4-7 mm). The multiple-adjusted OR for bleeding after EMR for depressed type of tumor was 4.21 (95%CI, 1.75-10.10) compared with elevated type. CONCLUSION: It is important to take tumor characteristics (tumor size and endoscopic pattern) and cutting method of EMR into consideration in predicting bleeding after EMR.     

血管抑肽(Angiopeptin)预防PTCA后及/或支架内再狭窄

血管抑肽（angiopeprin)，一种人工合成的环八肽，生长抑素（somatostatin)的类似物，在动物实验证实可抑制动脉损伤后的内膜增生、预防PTCA（经皮穿刺冠状动脉扩张成型术）后再狭窄，然而，预防PTCA后再狭窄的临床试验则有不同的结果。我们简要复习了近年文献，讨论了血管抑肽在预防PTCA后及支架内再狭窄的作用，分析了血管抑肽的给药途径与给药方法以及动物实验与临床试验的结果及其可能的原因。     

鲑鱼降钙素鼻喷剂治疗绝经后骨质疏松患者骨密度及骨转换指标的变化

目的 观察鼻喷鲑鱼降钙素(calcitonin)治疗绝经后骨质疏松症(postmenopausal osteoporosis,PMO)患者6个月和12个月后骨密度及骨转换指标的变化.方法 选择PMO患者共67例,给予鼻喷降钙素治疗37例;其余30例PMO患者单纯服用钙剂和维生素D作为对照组.各组分别于用药前和用药后6个月和12个月采用DEXA骨密度仪测定骨密度;定量夹心酶联免疫法(ELISA)测定Ⅰ型胶原N末端肽(NTX)、骨特异性碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶(TRACP-5b)、25-羟维生素D,化学发光法测定骨钙素(BGP).结果 5例患者因医疗费用、拒绝坚持治疗退出试验,鼻喷降钙素组共32例完成试验.鼻喷降钙素治疗6个月后可见患者股骨颈和腰椎骨密度均较前有所增加,但仅在腰椎差异有统计学意义(P＜0.05),而在股骨颈治疗前后骨密度的差异无统计学意义(P＞0.05).治疗12个月时股骨颈和腰椎骨密度较前均明显升高,差异有统计学意义(P＜0.05).对照组在治疗6个月时的腰椎和治疗12个月时的股骨颈和腰椎部位骨密度均较治疗前降低,差异有统计学意义(P＜0.05).鼻喷降钙素治疗6个月和12个月时,股骨颈和腰椎骨密度均较对照组升高(P＜0.05).鼻喷降钙素治疗6个月后,TRACP-5b、NTX/Cr较治疗前降低,差异有统计学意义(P＜0.05);治疗12个月后,除TRACP-5b、NTX/Cr较前降低更加明显以外(P＜0.01),BALP较治疗前有升高,差异有统计学意义(P＜0.05).对照组在治疗12个月时,BALP较前有降低,差异有统计学意义(P＜0.05).25-羟维生素D在各组经治疗后,均明显升高,差异有统计学意义.结论 本研究结果显示鼻喷降钙素治疗6个月有效,12个月效果显著,可预防骨丢失,增加骨量.

Abstract：

Objective To study the changes of bone mineral density(BMD)and bone turnover in postmenopausal osteoporotic patients treated with salmon calcitonin nasal spray. Methods Sixty-seven postmenopausal osteoporotic patients were enrolled in our trial. All of them received calcium and vitamin D; 37patients were treated with salmon calcitonin nasal spray for 12 months and the other 30 patients received calcium and vitamin D only. Dual-energy X-ray absorptiometry(DEXA)and measurements of a series of bone turnover indices were performed before and after medication for 6 and 12 months. Results After treatment with salmon calcitonin nasal spray for6 months, BMD in lumbar spine 2-4 increased but no change occurred in femoral neck. However, after treatment for 12 months, BMD in both lumbar spine 2-4 and femoral neck increased. In the control group, BMD in lumbar spine 2-4 decreased after treatment for 6 and 12 months, but BMD in femoral neck decreased only after 12months. Comparing with the control group, after treatment with salmon calcitonin nasal spray, BMD in lumbar spine 2-4 and femoral neck were increased obviously. The level of TRACP-5b and NTX/Cr decreased after treatment with salmon calcitonin nasal spray for6 months and 12 months, while BALP increased only after treatment for 12 months. In the control group, BALP decreased after treatment for 12 months. The level of 25-(OH)vitamin D increased after treatment for 6 months and 12 months in both groups. Conclusions Long-term treatment with salmon calcitonin nasal spray prevents bone loss and may increase bone mass.     

Valvotomy for isolated congenital aortic stenosis in children: prognostic factors for outcome.

Early and late results after surgery for isolated congenital valvar aortic stenosis were evaluated in a total of 86 children under 16 years of age (mean 7.4 years). Primary procedure was always conservative. There were 7/86 (8.1%) early deaths. All infants who died after the operation were younger than 4 months of age. Among the clinical variables tested by the univariate analysis only age and duration of cardiopulmonary bypass were significant prognostic factors for early death. There were 6/67 (7.7%) valve-related late deaths. Multivariate analysis could not identify any risk factors for early and late mortality. Actuarial survival was 97% (95% CL 93-101%) after 5 years, 94% (88-100%) after 10 years, 90% (82-98%) after 15 years, and 87% (77-97%) after 20 years. A total of 22/79 (28%) early survivors had a first reoperation and 5 had a second reoperation. Long follow-up interval was the only significant factor for reoperation. Actuarial reoperation-free interval was 91% (85-98%) after 5 years, 70% (58-81%) after 10 years, and 50% (34-64%) after 15 years. Significant factors for poor valve function were long duration of follow-up, endocarditis, and young age at operation. The probability of normal valve function was 91% (84-98%) after 5 years, 67% (55-79%) after 10 years, and 54% (40-68%) after 15 years.     

Outcome and long-term follow-up of alloreactive donor lymphocyte infusions given for relapse after myeloablative allogeneic hematopoietic stem cell transplantations (HSCT)

In order to study efficacy, toxicity and the long-term results of donor lymphocyte infusions (DLI), we retrospectively analyzed DLI given for relapse after conventional allogeneic hematopoietic stem cell transplantation (HSCT) in 30 patients with a median delay of 107.5 months after transplant and 58 months after DLI. After DLI, 15 patients established full donor chimerism, three patients developed grade III and one grade IV acute GVHD. A total of 15 patients achieved a disease response. Among the 14 patients with chronic myeloid leukemia (CML), 11 are alive at the last follow-up: five are in complete molecular response (CMR) and two in complete cytogenetic response (CCR) with no other intervention after DLI, three in CMR after imatinib mesylate given after DLI and one in complete hematological response after imatinib mesylate and reduced-intensity conditioning allogeneic SCT performed after DLI. At the time of the last follow-up, 19 (63%) patients died and 11 (37%) remain alive. The 3-year probability of survival for the entire population, CML patients and non-CML patients, was 60, 93, 62% after transplantation, and 48, 80 and 48% after DLI, respectively. A multivariate analysis demonstrated a significantly worse survival rate after transplantation for female recipients, advanced disease and acute leukemia before transplantation.     

Early and late effects of captopril treatment after large myocardial infarction in rats

The early (after 21 days) and late (after 4 months) effects of continuous treatment with captopril on left ventricular performance, weight and volumes were studied in rats with myocardial infarction. Early effects were examined in rats subjected to coronary ligation and randomized to either immediate treatment with captopril (2 g/liter drinking water) starting 2 h after surgery or no treatment. After 21 days, the treated group showed reductions in mean arterial, left ventricular systolic and left ventricular end-diastolic pressures compared with untreated rats. Right and left ventricular weight and left ventricular volumes were decreased and the ejection fraction index was increased by captopril treatment. To study the late effects of captopril, a second group of rats was randomized to immediate captopril treatment (starting 2 h after surgery), delayed captopril treatment (starting 21 days after surgery) or no treatment. When studied after 4 months of treatment, rats started on captopril treatment 2 h after infarction showed no differences compared with rats started on treatment 21 days after infarction. Treatment with captopril for 4 months produced changes that were similar to those in rats treated for 21 days. Captopril treatment improved hemodynamic function after myocardial infarction in rats examined after either 21 days or 4 months of treatment. The extent of the benefit was similar in the two treatment periods. Initiation of captopril therapy immediately after infarction did not appear to produce a greater effect than treatment started at 21 days after infarction in rats studied after the drug had been administered for 4 months.     

Clinical analysis of patients with hepatocellular carcinoma recurrence after living-donor liver transplantation

AIM: To evaluated patterns and outcomes of hepatocellular carcinoma(HCC) recurrence after living donor liver transplantation(LDLT).METHODS: From 2001 to 2014, 293 patients underwent LDLT for HCC at our transplant center. We retrospectively reviewed 54(18.4%) patients with HCC recurrence after LDLT. We evaluated patterns and outcomes of HCC recurrence after LDLT, with particular attention to the Milan criteria at transplantation, treatments for HCC-recurrent patients, and factors related to survival after HCC recurrence. Furthermore, we evaluated the efficacy of combination treatment of sorafenib and an mT OR inhibitor.RESULTS: The 1-, 2-, and 3-year overall survival rates after HCC recurrence were 41.1%, 20.5%, and 15.4%, respectively. The median time interval between LDLT and HCC recurrence was 6.5 mo. Although recurrence rates according to the Milan criteria at LDLT were significantly different, HCC recurrence patterns and survival rates after HCC recurrence were not significantly different between the two groups. Time to recurrence 12 mo(P = 0.048), multiple recurrences at HCC recurrence(P = 0.038), and palliative treatment for recurrent tumors(P = 0.003) were significant independent prognostic factors for poor survival after HCC recurrence in a multivariate analysis. The combination treatment of sorafenib and sirolimus showedsurvival benefits in the palliative treatment group(P = 0.005).CONCLUSION: Curative treatment for recurrent HCC after LDLT is the most important factor in survival rates after HCC recurrence and combination treatments of sorafenib and an m TOR inhibitor could have survival benefits in patients with HCC recurrence after LT in the palliative treatment group.     

Delivery of progenitors to the thymus limits T-lineage reconstitution after bone marrow transplantation

T-cell production depends on the recruitment of hematopoietic progenitors into the thymus. T cells are among the last of the hematopoietic lineages to recover after bone marrow transplantation (BMT), but the reasons for this delay are not well understood. Under normal physiologic conditions, thymic settling is selective and either CCR7 or CCR9 is required for progenitor access into the thymus. The mechanisms of early thymic reconstitution after BMT, however, are unknown. Here we report that thymic settling is briefly CCR7/CCR9-independent after BMT but continues to rely on the selectin ligand PSGL-1. The CCR7/CCR9 independence is transient, and by 3 weeks after BMT these receptors are again strictly required. Despite the normalization of thymic settling signals, the rare bone marrow progenitors that can efficiently repopulate the thymus are poorly reconstituted for at least 4 weeks after BMT. Consistent with reduced progenitor input to the thymus, intrathymic progenitor niches remain unsaturated for at least 10 weeks after BMT. Finally, we show that thymic recovery is limited by the number of progenitors entering the thymus after BMT. Hence, T-lineage reconstitution after BMT is limited by progenitor supply to the thymus.