Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

食管腺癌淋巴结转移与肿瘤侵及食管壁深度的关系

目的 对腺癌侵及食管壁深度与淋巴结转移的关系以及淋巴结转移对预后的影响进行分析研究.方法 澳大利亚弗林德斯大学医学中心自1985年～2003年,手术治疗食管腺癌121例.其中男101例,女20例.年龄36～80岁,平均62岁.本组手术切除率为96.7%（117/121例）.手术清扫淋巴结的数目每例为2～30个,平均8个.无淋巴结转移59例（48.8%）、有淋巴结转移62例（51.2%）.本组病例全部得到随访.结果 当肿瘤位于黏膜层或黏膜下层（T1）时,淋巴结转移的发生率为22.2%（10/45例）、平均淋巴结转移的个数为0.3个、＞4个淋巴结转移的比例为0（0/45例）;当肿瘤侵及食管周围组织（T4）时,淋巴结转移的发生率为85.7%（6/7例）、平均淋巴结转移的个数为5.1个、＞4个淋巴结转移的比例为71.4%（5/7例）,P＜0.05.无淋巴结转移组的5年生存率为52.9%、1～4个淋巴结转移组的5年生存率为11.5%、＞4个淋巴结转移组的5年生存率为0,P＜0.01.结论 肿瘤对食管壁侵及深度和淋巴结转移的发生率及淋巴结转移的数量之间存在正相关性.随着肿瘤对食管壁侵及深度的增加,淋巴结转移的发生率、平均淋巴结转移的数量和＞4个淋巴结转移的比例均增加.有无淋巴结转移和淋巴结转移的数量是影响远期生存率的一个重要因素.     

A study exploring the role of intercostal nerve damage in chronic pain after thoracic surgery

Objective: Our aim was to investigate the prevalence of intra-operative nerve damage and its association with chronic pain. Methods: Our prospective study of 33 patients used nerve conduction studies to assess intercostal nerve function during elective thoracic surgical procedures. We used two methods to study nerve conduction: pre-operative magnetic stimulation (in 10 patients) and intra-operative nerve conduction studies (in all patients) We correlated these findings with specific intra-operative parameters, pain and psychological questionnaires pre-op and 3 month post-op and altered cutaneous sensation. Results: Magstim (magnetic stimulation) assessments were not reliable and were therefore abandoned. Intraoperative intercostal nerve studies revealed two distinct patterns of nerve injury and also that nerve injury was less in those cases where a rib was not resected. However, intercostal nerve damage detected at the time of operation is not associated with chronic pain or altered cutaneous sensation at 3 months post-op. Conclusions: The study findings suggest that either the amount of intra-operative intercostal nerve damage is not indicative of long-term nerve damage or that there is a more significant cause for chronic pain other than intercostal nerve injury.     

Unplanned splenectomy during oesophagectomy does not affect survival.

OBJECTIVE: There are limited and conflicting data available concerning the incidence of inadvertent splenectomy and its impact on the outcome in patients who have undergone oesophagectomy. The aim of this study is to identify the factors associated with a likelihood of inadvertent splenectomy and its influence on early and long-term outcome in patients having oesophagectomy for oesophageal carcinoma. METHODS: A consecutive series of 738 oesophagectomies performed between 1991 and 2004 was analysed. In our practice, the spleen was removed only if damaged intraoperatively. Routine chemo- and immunoprophylaxis would subsequently be used. Multivariate analysis with logistic and Cox models determined significant variables. RESULTS: Of the 738 oesophagectomies, 48 (6.5%) had splenectomy. Neoadjuvant chemotherapy was administered to a minority of patients; none subsequently had splenectomy. There were significant differences between types of operation (Ivor-Lewis 18 (9.0%), left thoracolaparotomy 14 (9.9%) and left thoracophrenotomy 15 (3.9%), p=0.01). Splenectomy was more common with advanced N stage disease (OR=0.44 [0.20-0.95]; p=0.04). Splenectomy resulted in more blood transfusions (median, 2 units vs 0 units; p=0.03) more anastomotic leaks (7 [14.6%] vs 42 [6.1%]; p=0.02) but not an increase in pulmonary complications (p=0.64) or in-hospital mortality (1 [4.6%] vs 37 [5.4%]; p=0.30). Splenectomy did not significantly affect median survival (551 [332-770] days vs 627 [554-700] days; p=0.63). CONCLUSION: Although inadvertent splenectomy increased the morbidity of oesophagectomy, it did not impair survival. Type of operation and advanced N stage are important risks for splenectomy. Though best avoided, most of the consequences of splenectomy can be managed. An unexpected relationship between splenectomy and anastomotic leaks needs further investigation.     

Effectiveness of early orthodontic treatment with the Twin-block appliance: a multicenter, randomized, controlled trial. Part 1: Dental and skeletal effects.

This study evaluated the effectiveness of early orthodontic treatment with the Twin-block appliance for the developing Class II Division 1 malocclusion. This multicenter trial was carried out in the United Kingdom. A total of 174 children, aged 8 to 10 years old, with Class II Division 1 malocclusion were randomly allocated to receive treatment with a Twin-block appliance or to an untreated, control group. Data were collected at the start of the study and 15 months later. Results showed that early treatment with Twin-block appliances resulted in reduction of overjet, correction of molar relationships, and reduction in severity of malocclusion. Most of this correction was due to dentoalveolar change, but some was due to favorable skeletal change. Early treatment with the Twin-block appliance is effective in reducing overjet and severity of malocclusion. The small change in the skeletal relationship might not be considered clinically significant.     

Association Between Outpatient Follow-Up and Pediatric Emergency Department Asthma Visits

Background. The National Heart, Lung, and Blood Institute (NHLBI) guidelines recommend that patients receive a follow-up outpatient asthma visit after being discharged from an emergency department (ED) for asthma. Objective. To measure the frequency of follow-up outpatient asthma visits and its association with repeat ED asthma visit. Design. We conducted a retrospective cohort study of children with asthma using claims data from a university-based managed care organization from 01 1998 to 10 2000. We performed a multivariate survival analysis using Cox proportional hazards model to determine the effect of follow-up outpatient asthma visits on the likelihood of a repeat ED asthma visit, after controlling for severity of illness, patient age, gender, insurance, and the specialty of the primary care provider. Results: A total of 561 children had 780 ED asthma visits. Of these, 103 (17%) had a repeat ED asthma visit within 1 year. Almost two-thirds of children (66%) did not receive outpatient follow-up for asthma within 30 days of an ED asthma visit. Outpatient asthma visits within 30 days of an ED asthma visit are associated with an increased likelihood (relative risk = 1.80; 95% confidence interval 1.19, 2.72) for repeat ED asthma visits within 1 year. Conclusions. Most patients do not have outpatient follow-up after an ED asthma visit. However, those patients that present for outpatient follow-up have an increased likelihood for repeat ED asthma visits. For the primary care provider, these outpatient follow-up visits signal an increased risk that a patient will return to the ED for asthma and are a key opportunity to prevent future ED asthma visits.     

A novel mutation in the last exon of ATRX in a patient with α-thalassemia myelodysplastic syndrome

Abstract:  We describe a patient with acquired alpha-thalassemia myelodysplastic syndrome (ATMDS). A previously healthy 66-year-old man presented with hemoglobin of 9.3 g/dL, mean corpuscular volume 59 fL, and a bone marrow aspirate with increased erythroid precursors and hypolobulated megakaryocytes. Hemoglobin H inclusions were seen in most red cells after 1% brilliant cresyl blue supravital stain of the peripheral blood. At the molecular level, we identified of a novel mutation in the most 3' exon of the ATRX gene ( C GA→ T GA substitution in codon 2407) resulting in a premature termination codon (p.R2407X). This case provides further evidence for a link between ATRX mutations and ATMDS, and suggests a possible role for the conserved Q-box element in ATRX function.     

Previous weight loss experiences of bariatric surgery candidates: how much have patients dieted prior to surgery?

OBJECTIVE: To describe the dieting histories of bariatric surgery candidates. RESEARCH METHODS AND PROCEDURES: One hundred seventy-seven individuals with extreme obesity who sought bariatric surgery completed the Weight and Lifestyle Inventory, a self-report instrument that assesses several variables, including weight and dieting history. Patients' dieting histories were further explored with an aided recall during a preoperative behavioral/psychological evaluation performed by a mental health professional. RESULTS: Participants who completed the Weight and Lifestyle Inventory reported an average of 4.7 +/- 2.9 successful dieting attempts, defined as those that resulted in a loss of 10 lbs (4.5 kg) or more. These individuals reported a mean total lifetime weight loss of 61.1 +/- 41.3 kg. Despite these efforts, their weight increased from 89.4 +/- 27.4 kg at the time of their first diet (age 21.2 +/- 10.1 years) to 144.5 +/- 30.8 kg at the time they underwent their behavioral/psychological evaluation (age 43.0 +/- 11.0 years). Results of the aided recall revealed that participants had made numerous other efforts to lose weight that were unsuccessful. Self-directed diets and commercial programs were used more frequently. DISCUSSION: Individuals who sought bariatric surgery reported an extensive history of dieting, beginning in adolescence, that was not successful in halting progressive weight gain. Thus, the recommendation often made by insurance companies that patients delay surgery to attempt more conservative treatment options may be unwarranted, particularly in the presence of significant obesity-related comorbidities. Weight loss histories should be routinely examined during a behavioral evaluation to determine whether additional attempts at non-surgical weight loss are advisable. Future studies also are needed to explore the potential relationship between dieting history and postoperative outcome.     

Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose: a simple analysis by 13C NMR of urinary menthol glucuronide.

Menthol glucuronide was isolated from the urine of a healthy 70-kg female subject following ingestion of 400 mg of peppermint oil and 6 g of 99% [U-(13)C]glucose. Glucuronide (13)C-excess enrichment levels were 4-6% and thus provided high signal-to-noise ratios (SNRs) for confident assignment of (13)C-(13)C spin-coupled multiplet components within each (13)C resonance by (13)C NMR. The [U-(13)C]glucuronide isotopomer derived via direct pathway conversion of [U-(13)C]glucose to [U-(13)C]UDP-glucose was resolved from [1,2,3-(13)C(3)]- and [1,2-(13)C(2)]glucuronide isotopomers derived via Cori cycle or indirect pathway metabolism of [U-(13)C]glucose. In a second study, a group of four overnight-fasted patients (63 +/- 10 kg) with severe heart failure were given peppermint oil and infused with [U-(13)C]glucose for 4 hr (14 mg/kg prime, 0.12 mg/kg/min constant infusion) resulting in a steady-state plasma [U-(13)C]glucose enrichment of 4.6% +/- 0.6%. Menthol glucuronide was harvested and glucuronide (13)C-isotopomers were analyzed by (13)C NMR. [U-(13)C]glucuronide enrichment was 0.6% +/- 0.1%, and the sum of [1,2,3-(13)C(3)] and [1,2-(13)C(2)]glucuronide enrichments was 0.9% +/- 0.2%. From these data, flux of plasma glucose to hepatic UDPG was estimated to be 15% +/- 4% that of endogenous glucose production (EGP), and the Cori cycle accounted for at least 32% +/- 10% of GP.