Stem Cell Migration and Proliferation During Severe Anemia

The pluripotential stem cell (CFU) compartment of marrow and spleen wasevaluated in mice subjected to an intense erythroid stimulus associated withphenylhydrazine-induced anemia. Erythroid hyperplasia occurred in both marrow and spleen. CFU in the marrowgradually declined to approximately 50per cent of control levels (day 5) whiletheir numbers in the spleen increased(fourfold) by day 3 and were maintainedat this level for several days. Thesechanges in numbers of marrow andsplenic CFU were not associated withCFU proliferation. Thereafter, CFU inthe marrow, but not in the spleen, entered active cell cycle. The data suggestthat CFU migrate from marrow to spleenduring the demands of severe anemia.The induction of marrow CFU into cyclefurther suggests a negative feedback,which, perhaps through cell-cell interaction, maintains stem cells at a criticalcompartment size. The failure of splenicCFU to cycle may reflect the converseeffect, i.e. an inhibition on stem cell proliferation in the wake of an expandedstem cell pool.

Submitted on March 17, 1970 Revised on May 14, 1970 Accepted on June 9, 1970     

Removal of primary tumor improves survival in metastatic breast cancer. Does timing of surgery influence outcomes?

Background

Resection of intact primary tumor is controversial in metastatic breast cancer patients. The aim of this study is to review the impact of surgical resection of primary tumor on overall survival and to assess the role of timing of surgery on survival rates.

Methods

208 patients with metastatic breast cancer diagnosed between 1982 and 2005 in the Hospital Clinico of Valencia (Spain) were analysed. Exclusion criteria were age >80, PS 3–4, Charlson score 3 or follow-up < 90 days. 123 of these underwent surgery and 85 did not. In order to assess the role of timing, the "surgery" cohort was divided into two sub-groups: "before" (n = 78) or "after" (n = 45) diagnosis of disseminated disease.

Results

In the surgery group, patients underwent mastectomy with axillary dissection (82.9%), without axillary dissection (8.9%) and conservative surgery (8.1%). After a median follow-up of 29.68 months, median OS in the "surgery" and the "non-surgery" groups were, 40.4 and 24.3 months. Removal of the primary tumor therefore had a significant positive impact on survival rates (p < 0.001). Benefits of surgery were observed mainly in patients with visceral disease (p = 0.005); no statistical differences were found in those with bone disease (p = 0.79). Univariate analysis for overall survival (OS) identified surgery, performance status, clinical T stage, hormone receptors and number and type of metastases as variables that impacted on survival. In the multivariate test, only resection of primary tumor and estrogen receptors maintained statistical significance, surgery having a protective effect with an HR 0.52 (95% CI 0.35–0.77). No differences in survival were found between the two sub-groups according to the timing of surgery: "before" vs "after"(p = 0.996).

Conclusions

Resection of primary tumor should be considered not only as a palliative or preventive strategy but also as an approach that possibly contributes to the control of the disease in selected patients.     

Partial excision of scaphoid: is it ever indicated?

The carpal scaphoid cannot be partially or totally excised without paying a functional penalty, usually in the form of carpal instability. In selected conditions, however, a partial scaphoidectomy may be preferred over other less reliable alternatives. These include excision of a small fragment of a fractured proximal pole when there is no injury to the scapholunate ligaments; excision of the distal fragment of a nonunited, arthritic distal-third scaphoid fracture; resection-arthroplasty of isolated STT osteoarthritis; and distal scaphoid excision to improve midcarpal function after a radioscapholunate fusion. In this article, both the pathomechanics and clinical results of such techniques are discussed.     

LOWER POLE I: A PROSPECTIVE RANDOMIZED TRIAL OF EXTRACORPOREAL SHOCK WAVE LITHOTRIPSY AND PERCUTANEOUS NEPHROSTOLITHOTOMY FOR LOWER POLE NEPHROLITHIASIS—INITIAL RESULTS

PURPOSE: The efficacy of shock wave lithotripsy and percutaneous stone removal for the treatment of symptomatic lower pole renal calculi was determined. MATERIALS AND METHODS: A prospective randomized, multicenter clinical trial was performed comparing shock wave lithotripsy and percutaneous stone removal for symptomatic lower pole only renal calculi 30 mm. or less. RESULTS: Of 128 patients enrolled in the study 60 with a mean stone size of 14.43 mm. were randomized to percutaneous stone removal (58 treated, 2 awaiting treatment) and 68 with a mean stone size of 14.03 mm. were randomized to shock wave lithotripsy (64 treated, 4 awaiting treatment). Followup at 3 months was available for 88% of treated patients. The 3-month postoperative stone-free rates overall were 95% for percutaneous removal versus 37% lithotripsy (p <0.001). Shock wave lithotripsy results varied inversely with stone burden while percutaneous stone-free rates were independent of stone burden. Stone clearance from the lower pole following shock wave lithotripsy was particularly problematic for calculi greater than 10 mm. in diameter with only 7 of 33 (21%) patients becoming stone-free. Re-treatment was necessary in 10 (16%) lithotripsy and 5 (9%) percutaneous cases. There were 9 treatment failures in the lithotripsy group and none in the percutaneous group. Ancillary treatment was necessary in 13% of lithotripsy and 2% percutaneous cases. Morbidity was low overall and did not differ significantly between the groups (percutaneous stone removal 22%, shock wave lithotripsy 11%, p =0.087). In the shock wave lithotripsy group there was no difference in lower pole anatomical measurements between kidneys in which complete stone clearance did or did not occur. CONCLUSIONS: Stone clearance from the lower pole following shock wave lithotripsy is poor, especially for stones greater than 10 mm. in diameter. Calculi greater than 10 mm. in diameter are better managed initially with percutaneous removal due to its high degree of efficacy and acceptably low morbidity.     

Pilot study of a novel pain management strategy: evaluating the impact on patient outcomes

Background

Our objective was to evaluate the impact of a novel multimodal pain management strategy on intraoperative opioid requirements, postoperative pain, narcotic use, and length of stay.

Methods

Consecutive patients undergoing elective laparoscopic colorectal resection were managed with an experimental protocol. The protocol uses a post-induction, pre-incision bilateral TAP block and local peritoneal infiltration at port sites with long-acting liposomal bupivacaine (20 mL long-acting liposomal bupivacaine, 30 mL 0.25 % bupivacaine, 30 mL saline). Experimental patients were matched on age, body mass index, gender, comorbidity, diagnosis, and procedure to a control group that received no block or local wound infiltration. Both groups followed a standardized enhanced recovery pathway. Demographics, perioperative, and postoperative outcomes were evaluated. The main outcome measures were intraoperative opioids, postoperative pain, opioid use, and length of stay.

Results

Fifty patients were analyzed—25 experimental and 25 controls. Patients were well matched on all demographics. In both cohorts, the main diagnosis was colorectal cancer and primary procedure performed a segmental resection. Operative times were similar (p = 0.41). Experimental patients received significantly less intraoperative fentanyl (mean 158 mcg experimental vs. 299 mcg control; p < 0.01). The experimental group had significantly lower initial (p < 0.01) and final PACU pain scores (p = 0.04) and shorter LOS (3.0 vs. 4.1 days, p = 0.04) compared to controls. Experimental patients trended toward shorter PACU times and lower opioid use and daily pain scores throughout the hospital stay. Postoperative complication and readmission rates were similar across groups. There were no reoperations or mortality.

Conclusions

Our multimodal pain management strategy reduced intraoperative opioid administration. Postoperatively, improvements in PACU time, postoperative pain and narcotic use, and lengths of stay were seen in the experimental cohort. With the favorable finding from the pilot study, further investigation is warranted to fully evaluate the impact of this pain management protocol on patient satisfaction, clinical and financial outcomes.

     

单核细胞向巨噬细胞分化过程中CD44mRNA表达和黏附功能的变化

目的探讨单核细胞向巨噬细胞分化过程中CD44 mRNA表达和黏附功能的变化。方法应用豆蔻佛波醇乙酯(PMA)诱导单核细胞系U937向巨噬细胞分化;应用RT-PCR分析U937细胞CD44 mRNA表达变化,并以β-actin作为内参进行半定量评价,并对主要条带进行测序;应用荧光染料BCECF/AM作为探针,测定黏附于激活的内皮细胞上的U937细胞数目。结果与对照组比较,PMA诱导的U937细胞CD44 mRNA总体表达显著增加(P=0.01037),异构体/标准CD44比例显著上升(P=0.0005551),测序结果显示PMA刺激后显著增加的是947 bp(V8 V9 V10)和1208 bp(V7 V8 V9 V10)CD44异构体。同时,PMA刺激后U937细胞黏附功能显著增加(P=0.0029)。结论单核细胞向巨噬细胞分化过程中CD44 mRNA,特别是947bp(V8 V9 V10)和1208 bp(V7 V8 V9 V10)CD44异构体的表达显著增加,可能与细胞黏附功能的增强相关。     

RNA Synthesis in Cultures of Normal Human Peripheral Blood

RNA and DNA synthesis were measured in cultures of normal human peripheral blood using tritiated cytidine and thymidine and autoradiographictechnics. RNA synthesis preceded DNA synthesis by 24 hours. RNA synthesisoccurred predominantly in the large and medium-sized "blast-like" cells, butdid occur, to a lesser extent, in the small lymphocytes. RNA synthesis did notoccur in the absence of phytohemagglutinin, nor did DNA synthesis. Mechanisms of action of phytohemagglutinin are discussed with particular referenceto its possible antigenic nature.

Submitted on August 12, 1963 Accepted on January 6, 1964     

PRETREATMENT WITH PARACETAMOL INHIBITS METABOLISM OF ENFLURANE IN RATS

We studied the interaction between paracetamol (acetaminophenU.S.P.) and enflurane. Sixteen rats were assigned to four groups(n=4) to receive: paracetamol 7.5 mg/100 g body weight; paracetamolplus 1% enflurane; 1% enflurane alone, or no treatment (controls).Animals were killed 6 h later. A second series of 16 were treatedidentically, but were killed after 24 h. Measurements were madeof fluoride concentrations in serum, liver and urine (indicatorsof biotransformation of enflurane), paracetamol concentrationsin urine, pathological changes in liver samples, and concentrationsof the enzymes aspartate aminotransferase (AST) and alanineaminotransferase (ALT) in serum. Pretreatment with paracetamolsignificantly decreased urinary fluoride at 6 and 24 h afterexposure to enflurane, but decreased fluoride concentrationsin serum and liver only at 6 h after exposure to enflurane.Paracetamol concentrations in urine did not change after exposureto enflurane. Exposure to paracetamol alone increased AST andALT. At 24 h after exposure to enflurane, serum concentrationsof enzymes in rats pretreated with paracetamol were similarto those of control rats. Pretreatment with paracetamol maytherefore inhibit metabolism of enflurane. Although no hepaticdamage was observed, the increased in AST and AL T suggestedsubclinical liver damage in rats given only paracetamol.