Progressive platelet activation with storage: evidence for shortened survival of activated platelets after transfusion

Platelets are known to become activated during storage, but it is unclear whether such activation affects recovery or survival after platelet concentrate (PC) transfusion. With the use of flow cytometry to determine the percentage of platelets expressing the alpha-granule membrane protein 140 (GMP-140), a known adhesive ligand appearing on the platelet surface after activation, several studies were conducted. These investigations evaluated 1) the occurrence of significant platelet activation over time in PCs (n = 46) stored under standard blood bank conditions; 2) the correlation between platelet activation and platelet recovery in normal subjects after PC storage (n = 12), as assessed by the recovery of Indium-labeled platelets; and 3) the recovery of activated and unactivated platelets in thrombocytopenic cancer patients transfused with standard PCs (n = 11). It was determined 1) that an increasing duration of storage of PC was associated with increasing platelet activation as measured by the percentage of platelets expressing GMP-140, progressing from a mean of 4 +/- 2 percent (SD) on the day of collection to a mean of 25 +/- 8 percent by 5 days of storage: 2) that, in normal subjects, posttransfusion recovery of autologous platelets stored for 2 to 4 days and then labeled with In111 was inversely correlated with the percentage of activated platelets in the transfused PC (r = -0.55, p = 0.05); and 3) that, when thrombocytopenic patients were transfused with standard PCs, the recovery of the activated platelets in the transfused PCs averaged only 38 +/- 15 percent of the number predicted by the absolute platelet increment.(ABSTRACT TRUNCATED AT 250 WORDS)     

细胞移植治疗帕金森病的研究进展

目的:根据近年细胞移植治疗帕金森病的近况,认识细胞移植治疗帕金森病的最新进展及临床应用前必须解决的技术难题。资料来源:应用计算机检索Pubmed 2000-01/2006-10细胞移植治疗帕金森病的文章,检索词为"Cells transplantation,Parkinson disease",并限定文献种类为English。资料选择:对资料进行初审,选取包括细胞移植与帕金森病相关的文献,开始查找全文。纳入标准:①细胞移植在神经系统疾病中的应用。②细胞移植与帕金森病。排除标准:综述文献、重复研究、Meta分析类文章。资料提炼:共收集到175篇关于细胞移植与帕金森病的文献,纳入30篇文献。资料综合:细胞移植治疗帕金森病的主要细胞来源有肾上腺髓质细胞、胎儿中脑腹侧组织细胞、异种移植、神经干细胞、骨髓干细胞、胚胎干细胞等。其临床应用前仍存在许多技术难题,如移植物的来源、移植部位与方法、移植环境等。随着这些基础研究和临床治疗上难题的解决,细胞移植必将成为治疗帕金森病的重要手段。结论:细胞移植尤其是胚胎干细胞的应用,将为帕金森病的治疗带来新的曙光。     

High-energy phosphates,myocardial contractile function and material properties after short periods of oxygen deficiency

Summary To investigate myocardial performance and diastolic properties after repeated periods of oxygen deficiency auxotonic and isovolumic measurements were performed after three periods (4 min) of asphyxia in Wistar rats (n=19). Additionally, the response of the peak isovolumic left ventricular pressure to postextrasystolic potentiation was measured. The hemodynamic results were compared to the levels of high-energy phosphates.Already after 15 min of recovery from asphyxia auxotonic measures of systolic function were completely normal compared to the control group (n=19). Isovolumic measurements after 20 min of postasphyctic recovery, however, demonstrated a considerable reduction of the peak left ventricular pressure (226.5±7.5 mm Hg vs. 262.6±3.4 mm Hg in controls, mean±SEM (p<0.01)) indicating persistence of decreased postischemic contractile performance. The relative effect of postextrasystolic potentiation was similar in both groups, but could not compensate for the reduced performance of the postasphyctic hearts: the absolute postextrasystolic peak isovolumic pressure of the postasphyctic hearts was lower than the value of the regular isovolumic peak pressure in the controls. Diastolic properties (pressure/volume and stress/strain relationships) of the postasphyctic myocardium remained unchanged. The total sum of the adenine-nucleotides decreased from 7.2±0.2 to 5.6±0.3 mol/gww (p<0.01). ATP was reduced from 4.8±0.2 to 3.9±0.3 mol/gww (p<0.01). Phosphocreatine was elevated to 7.0±0.6 mol/gww, x±SEM (p<0.01).Our results demonstrated normal postasphyctic basal hemodynamics and material properties. Thus, the energy supply was sufficient to maintain steady state conditions — in spite of decreased overall adenine-nucleotide levels. Isovolumic measurements and postextrasystolic potentation tests, however, indicated that the contractile performance of the postischemic myocardium was still reduced. This functional limitation cannot be explained by altered material properties and is probably not causally related to the decreased overall ATP content.Parts of the results were presented at the 10th World Congress of Cardiology, Washington D.C., USA, 1986Supported by the Deutsche Forschungsgemeinschaft (DFG), Bonn (Ho 1003/1-1)     

Detection and viability of tumor cells in peripheral blood stem cell collections from breast cancer patients using immunocytochemical and clonogenic assay techniques [see comments]

Although peripheral blood stem cell collections (PBSC) are thought to have less tumor involvement than bone marrow (BM), the incidence of circulating tumor cells in patients with breast cancer has not been widely investigated. We prospectively investigated the incidence and viability of tumor cell involvement in PBSC and BM collections from breast cancer patients undergoing high-dose chemotherapy/hematopoietic stem cell transplantation. Paired samples of PBSC and BM from 48 patients were analyzed using an immunocytochemical technique that detects one epithelial-derived tumor cell per 5 x 10(5) mononuclear cells. Immunostained tumor cells were detected in 9.8% (13/133) PBSC specimens from 9/48 (18.7%) patients and in 62.3% (38/61) BM specimens from 32/48 (66.7%) patients, a significantly higher rate than in PBSC (P < .005). The geometric mean concentration of tumor cells in contaminated PBSC specimens was 0.8/10(5) mononuclear cells (range 0.33 to 2.0/10(5)) compared with 22.9/10(5) mononuclear cells in BM (range 1 to 3,000/10(5), P < .0001). In culture experiments, clonogenic tumor colonies grew in 21/26 immunocytochemically positive specimens. No tumor colony growth was detected in 30/32 immunocytochemically negative specimens. Immunocytochemical detection of tumor involvement in BM and PBSC correlated significantly with in vitro clonogenic growth (P < .0001). We conclude that PBSC contain fewer tumor cells than paired BM specimens from patients with advanced breast cancer and that these tumor cells appear to be capable of clonogenic growth in vitro.     

IgG4‐related sialadenitis and Sjögren's syndrome

IgG4‐related disease (IgG4‐RD) has emerged as a new entity in the last decade. It comprises numerous conditions previously thought to be unrelated. Macroscopically, these diseases cause diffuse organ swelling and formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with increased IgG4+ plasma cells and storiform fibrosis. Despite rapid progress within the last years, our knowledge on these conditions is still fragmented. To date, more than forty organs have been reported to be included in IgG4‐RD, and salivary gland involvement is amongst the most common organs affected [IgG4‐related sialadenitis (IgG4‐RS)]. Interestingly, IgG4‐RS shares commonalities with Sjögren's syndrome (SS), like glandular enlargement, sicca symptoms, arthralgias, hypergammaglobulinemia, hypocomplementemia, and circulating antinuclear antibodies. Nonetheless, they differ in that the incidence of anti‐Ro and anti‐La reactivity is not frequently found in patients with IgG4‐RS, their salivary glands are infiltrated by a large number of IgG4+ plasma cells and IgG4‐RS symptoms respond promptly to steroids. The aim of this review was to describe the clinical, serological, histopathological and pathophysiological aspects of IgG4‐RS in the context of IgG4‐RD and highlight the differences between IgG4‐RS and SS.     

Treatment of progressive Hodgkin's disease with intensive chemoradiotherapy and autologous bone marrow transplantation

Twenty-six patients with progressive Hodgkin's disease after conventional chemotherapy received intensive chemoradiotherapy and autologous bone marrow transplantation (ABMT); 19 also received additional involved-field radiotherapy. Twenty-one patients [81%, 95% confidence intervals (CI) 61% to 94%] attained complete (n = 18) or partial responses. Ten patients (38%, 95% CI 20% to 59%) are disease- free a median of 4.5 years later (range 3.5 to 7.0 years), including seven patients with continuous complete responses. The likelihood of overall response was not significantly influenced by any clinical or treatment variable examined. However, there was a trend favoring patients with higher Karnofsky scores, and higher scores were associated with attainment of complete responses (P = .06 and P = .02, respectively, Mann-Whitney U test). Both higher Karnofsky scores and shorter durations of disease before transplantation were associated with improved survival in a stepwise Cox multivariate analysis. The chief cause of failure was progression at sites previously involved with Hodgkin's disease. No patient relapsed in the marrow, and two of three patients with a history of marrow involvement with Hodgkin's disease achieved durable complete responses after transplantation. These data suggest that inadequate pretransplant conditioning, and not the reinoculation of occult tumor cells in the autologous marrow, caused most relapses. Fatal treatment-related toxicity occurred in six patients. Three patients died of idiopathic interstitial pneumonitis; each had previously received local mediastinal irradiation before intensive chemoradiotherapy. Intensive chemoradiotherapy and ABMT produces durable responses in some patients with Hodgkin's disease incurable with conventional therapy. Use of such therapies at the first sign of failure with conventional chemotherapy and development of more effective conditioning regimens should further improve results.     

Lymph node count and prognosis in colorectal cancer: The influence of examination quality

Colorectal cancer guidelines recommend adjuvant chemotherapy in stage II disease when less than 12 lymph nodes are assessed. The recommendation bases on previous studies showing an association of a low lymph node count and adverse outcome. Compared to current standards, however, the quality of lymph node examination in the studies was low. We, therefore, investigated the prognostic role of <12 lymph nodes in cancers diagnosed adherent to current quality measures. Stage I–IV colorectal cancers from 1,899 patients enrolled into a population‐based cohort study were investigated for the prognostic impact of a lymph node count <12. The stage specific share of patients diagnosed with ≥12 nodes (stage I–IV: 62, 85, 85, 78%, respectively) was used to compare lymph node examination quality to other studies. We found no impact of a lymph node count <12 on overall, cancer‐specific or recurrence‐free survival for any tumour stage. Compared to studies reporting an adverse prognostic impact of a low lymph node count in stages II and III the stage‐specific shares of patients with ≥12 nodes were markedly higher in this study (85% vs. 24–58% in previous analyses) and this correlated with increased rates of stage III compared to stage II cancers. In conclusion our data indicate, that the previously reported effect of a low lymph node count on the patients' outcomes is eliminated by improved lymph node examination quality and thus question the general applicability of a 12 lymph node cut off for adjuvant chemotherapy decision making in stage II disease.     

Smoking and survival of colorectal cancer patients: Population‐based study from Germany

Current evidence on the association between smoking and colorectal cancer (CRC) prognosis after diagnosis is heterogeneous and few have investigated dose‐response effects or outcomes other than overall survival. Therefore, the association of smoking status and intensity with several prognostic outcomes was evaluated in a large population‐based cohort of CRC patients; 3,130 patients with incident CRC, diagnosed between 2003 and 2010, were interviewed on sociodemographic factors, smoking behavior, medication and comorbidities. Tumor characteristics were collected from medical records. Vital status, recurrence and cause of death were documented for a median follow‐up time of 4.9 years. Using Cox proportional hazards regression, associations between smoking characteristics and overall, CRC‐specific, non‐CRC related, recurrence‐free and disease‐free survival were evaluated. Among stage I–III patients, being a smoker at diagnosis and smoking ≥15 cigarettes/day were associated with lower recurrence‐free (adjusted hazard ratios (aHR): 1.29; 95% confidence interval (CI): 0.93–1.79 and aHR: 1.31; 95%‐CI: 0.92–1.87) and disease‐free survival (aHR: 1.26; 95%‐CI: 0.95–1.67 and aHR: 1.29; 95%‐CI: 0.94–1.77). Smoking was associated with decreased survival in stage I–III smokers with pack years ≥20 (Overall survival: aHR: 1.40; 95%‐CI: 1.01–1.95), in colon cancer cases (Overall survival: aHR: 1.51; 95%‐CI: 1.05–2.17) and men (Recurrence‐free survival: aHR: 1.51; 95%‐CI: 1.09–2.10; disease‐free survival: aHR: 1.49; 95%‐CI: 1.12–1.97), whereas no associations were seen among women, stage IV or rectal cancer patients. The observed patterns support the existence of adverse effects of smoking on CRC prognosis among nonmetastatic CRC patients. The potential to enhance prognosis of CRC patients by promotion of smoking cessation, embedded in tertiary prevention programs warrants careful evaluation in future investigations.     

Cost-effectiveness of counseling and pedometer use to increase physical activity in the Netherlands: a modeling study

Background

Counseling in combination with pedometer use has proven to be effective in increasing physical activity and improving health outcomes. We investigated the cost-effectiveness of this intervention targeted at one million insufficiently active adults who visit their general practitioner in the Netherlands.

Methods

We used the RIVM chronic disease model to estimate the long-term effects of increased physical activity on the future health care costs and quality adjusted life years (QALY) gained, from a health care perspective.

Results

The intervention resulted in almost 6000 people shifting to more favorable physical-activity levels, and in 5100 life years and 6100 QALYs gained, at an additional total cost of EUR 67.6 million. The incremental cost-effectiveness ratio (ICER) was EUR 13,200 per life year gained and EUR 11,100 per QALY gained. The intervention has a probability of 0.66 to be cost-effective if a QALY gained is valued at the Dutch informal threshold for cost-effectiveness of preventive intervention of EUR 20,000. A sensitivity analysis showed substantial uncertainty of ICER values.

Conclusion

Counseling in combination with pedometer use aiming to increase physical activity may be a cost-effective intervention. However, the intervention only yields relatively small health benefits in the Netherlands.     

Tolerance of myocardium of aged animals to repeated oxygen deficiency

Summary Hemodynamic and metabolic effects of three times 4 min of oxygen deficiency were investigated in 18-month-old rats in comparison to 4-month-old Wistar rats. Left-ventricular isovolumicpressure-generating capacity and dp/dt_max during isovolumic conditions and hemodynamic indices during intact circulation were determined in open-chest rats. Additionally, high-energy phosphates were measured at the end of the experiments after 20 min of postasphyxial recovery.Older rats had a significantly reduced isovolumic left-ventricular pressure generating capacity (236±9 vs 269±5 mm Hg; p<0.05) and a low cardiac index (55±9 vs 117±8 ml×min^–1×kg^–1). The effects of the oxygen deficiency were comparable in both groups. The isovolumic pressure generating capacity was reduced for 11% vs 14%, and dp/dt_max for 13% vs 13%. The myocardial ATP-content was also decreased for the same extent in both groups (0.6 vs 1.0 mol/gww). Both hemodynamic and biochemical results indicate that aged myocardium does not have a reduced tolerance to repeated periods of oxygen deficiency.Supported in part by the Deutsche Forschungsgemeinschaft, Bonn, FRG (HO 1003/1-2)Parts of the results were presented at the 10th meeting of the Internat. Soc. for Heart Research (Europ. Section), Rotterdam, 1989