Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients

High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.     

Quality control of multidrug resistance assays in adult acute leukemia: correlation between assays for P-glycoprotein expression and activity

We have compared multiple assays for the P-glycoprotein (Pgp/MDR1) phenotype in fresh and thawed adult acute leukemia to validate and quantitate measures for the expression and function of Pgp. The results are related to the Pgp-expressing KB8 and KB8-5 call lines. The most sensitive assay was the measurement of modulation of the rhodamine 123 (R123) fluorescence by 2 micromol/L PSC833, followed by the modulation of the probe calcein-AM. We also found a good intralaboratory and interlaboratory correlation between the values of the R123/PSC833 assay for fresh as well as thawed samples. In addition, the affects of PSC833 on 3H-daunorubicin (DNR) accumulation, DNR fluorescence, and 3H- vincristine accumulation were very similar. The correlation between the DNR/PSC833 and R123/PSC833 test was r = .86 (N = 51). The modulation of drug accumulation by 8 micromol/L verapamil was the some as the PSC833 effect for DNR (117%, N = 21), but was higher for vincristine in every single case (161% v 121%, N = 22; P< .001), indicating additional verapamil effects, not related to Pgp. The correlation of the staining of viable cells for Pgp with the monoclonal antibody MRK16 was r = .77 (N = 52) for the R123/PSC833 functional test and r = .84 (N = 50) for the DNR/PSC833 test. From these results it could be calculated that a maximal increase of the mean DNR accumulation of about 50% can be achieved by blocking Pgp pump activity with PSC833 in leukemic blast samples with the highest mean Pgp expression. Subpopulations of blast calls with higher Pgp activity are likely to be present. Their relevance has to be studied further. The methods outlined here allow the reliable, quantitative monitoring of the Pgp/MDR1 phenotype in leukemias in multicentered, clinical Pgp modulation studies.     

Breast cancer: Current and future endocrine therapies

Endocrine therapy forms a central modality in the treatment of estrogen receptor positive breast cancer. The routine use of 5 years of adjuvant tamoxifen has improved survival rates for early breast cancer, and more recently has evolved in the postmenopausal setting to include aromatase inhibitors. The optimal duration of adjuvant endocrine therapy remains an active area of clinical study with recent data supporting 10 years rather than 5 years of adjuvant tamoxifen. However, endocrine therapy is limited by the development of resistance, this can occur by a number of possible mechanisms and numerous studies have been performed which combine endocrine therapy with agents that modulate these mechanisms with the aim of preventing or delaying the emergence of resistance. Recent trial data regarding the combination of the mammalian target of rapamycin (mTOR) inhibitor, everolimus with endocrine therapy have resulted in a redefinition of the clinical treatment pathway in the metastatic setting. This review details the current endocrine therapy utilized in both early and advanced disease, as well as exploring potential new targets which modulate pathways of resistance, as well as agents which aim to modulate adrenal derived steroidogenic hormones.     

Risk and predictors of dyssynchrony cardiomyopathy in left bundle branch block with preserved left ventricular ejection fraction

BackgroundLeft bundle branch block (LBBB) and left ventricular (LV) dyssynchrony likely contribute to progressive systolic dysfunction. The evaluation of newly recognized LBBB includes screening for structural heart abnormalities and coronary artery disease (CAD). In patients whose LV ejection fraction (EF) is preserved during initial testing, the incidence of subsequent cardiomyopathy is not firmly established.HypothesisThe risk of developing LV systolic dysfunction among LBBB patients with preserved LVEF is high enough to warrant serial imaging.MethodsWe screened records of 1000 consecutive patients with LBBB from our ECG database and identified subjects with an initially preserved LVEF (≥45%) without clinically relevant CAD or other cause for cardiomyopathy. Baseline imaging, clinical data, and follow‐up imaging were recorded to determine the risk of subsequent LV systolic dysfunction (LVEF ≤40%).Results(Data are mean + SD) 784 subjects were excluded, the majority for CAD or depressed LVEF upon initial imaging. Of the remaining 216, 37 (17%) developed a decline in LVEF(≤40%) over a mean follow‐up of 55 ± 31 months; 94% of these patients had a baseline LVEF≤60% and LV end systolic diameter (ESD) ≥ 2.9 cm indicating that these measures may be useful to define which patients warrant longitudinal follow‐up. The negative predictive value of a LVEF>60% and LVESD <2.9 cm was 98%.ConclusionsSeventeen percent of patients with LBBB and initial preserved LVEF develop dyssynchrony cardiomyopathy. We believe the risk of developing dyssynchrony cardiomyopathy is high enough to warrant serial assessment of LV systolic function in this high‐risk population.     

Hand,foot and mouth disease in China: evaluating an automated system for the detection of outbreaks

Objective

To evaluate the performance of China’s infectious disease automated alert and response system in the detection of outbreaks of hand, foot and mouth (HFM) disease.

Methods

We estimated size, duration and delay in reporting HFM disease outbreaks from cases notified between 1 May 2008 and 30 April 2010 and between 1 May 2010 and 30 April 2012, before and after automatic alert and response included HFM disease. Sensitivity, specificity and timeliness of detection of aberrations in the incidence of HFM disease outbreaks were estimated by comparing automated detections to observations of public health staff.

Findings

The alert and response system recorded 106 005 aberrations in the incidence of HFM disease between 1 May 2010 and 30 April 2012 – a mean of 5.6 aberrations per 100 days in each county that reported HFM disease. The response system had a sensitivity of 92.7% and a specificity of 95.0%. The mean delay between the reporting of the first case of an outbreak and detection of that outbreak by the response system was 2.1 days. Between the first and second study periods, the mean size of an HFM disease outbreak decreased from 19.4 to 15.8 cases and the mean interval between the onset and initial reporting of such an outbreak to the public health emergency reporting system decreased from 10.0 to 9.1 days.

Conclusion

The automated alert and response system shows good sensitivity in the detection of HFM disease outbreaks and appears to be relatively rapid. Continued use of this system should allow more effective prevention and limitation of such outbreaks in China.     

Depression and painful conditions: patterns of association with health status and health utility ratings in the general population

Purpose

Preference-weighted HRQoL (utility) ratings are increasingly used to guide clinical and resource allocation decisions, but their performance has not always been adequately explored. We sought to examine patterns of health utility ratings in community populations with depressive disorders and painful conditions.

Methods

We used two Canadian cross-sectional health surveys that obtained Comprehensive Health Status Measurement System/Health Utilities Index Mark 3 (HUI3) ratings and identified people with painful conditions and major depression. We estimated the frequency of item endorsements and mean utility ratings in these groups.

Results

Interesting differences between health state ratings and diagnostic categories were noted. For example, 71 % of those professionally diagnosed with migraine reported that they usually have “no pain.” Despite this, utility ratings were lower in those respondents with depressive episodes and in those with painful conditions. Greater than additive reductions in HUI3 scores were noted in most instances where both depressive disorders and painful conditions were present.

Conclusions

Health utility ratings confirm the clinical impression that painful conditions and depressive disorders magnify each other’s impact. Despite weak alignment between the health state definitions incorporated into utility ratings and the diagnostic concepts examined, the HUI3 appeared to capture HRQoL decrements and negative synergies associated with the co-occurrence of depressive episodes and painful conditions.     

儿童癌症幸存者成年后的慢性疾病

由于治疗方法的进步,近80%的儿童和青少年癌症患者能够长期生存。在美国,约有270000例儿童癌症的幸存者,即每640名20至39岁成年人中就有一名幸存者。大量的幸存者有利于儿童癌症治疗后长期健康结果的研究。现在可以明确的是,化疗和放疗所致的儿童各器官系统损害在临床上可能潜伏多年。为了全面了解治疗儿童癌症而继发的健康问题,重要的是衡量三项长期结果:健康状况、死亡率和患病率。这三项中,关于前两项已有相当好的研究报道。在一项对20227例癌症5年生存者的回顾性分析中,Mertens等发现以下原因导致的超额死亡率具有统计学意义:继发癌症(…     

腹腔镜外科和妇科联合手术的临床应用

目的：探讨腹腔镜技术在外科和妇科疾病治疗中联合应用的临床价值。　
方法：总结近7年来施行腹腔镜联合手术治疗妇、外科疾病229例的临床资料,其中腹腔镜胆囊切除术(laparoscopic cholecystectomy,LC)联合输卵管造口术5例,LC联合卵巢囊肿剥除术28例,LC联合子宫肌瘤剔除术25例,LC联合子宫次全切除术39例,LC联合子宫全切除术26例,LC联合子宫内膜异位症手术6例;腹腔镜阑尾切除术(laparoscopicappendectomy,LA)联合输卵管手术38例,LA联合卵巢囊肿切除术32例,LA联合子宫全切除术或子宫次全切除术24例,腹腔镜肝囊肿开窗引流术联合卵巢囊肿切除术6例。
结果：229例妇、外科联合腹腔镜手术均获成功,无中转开腹手术。手术时间40~220 min,平均120 min;住院1~6 d,平均3.4 d。仅1例术后10 d阴道残端出血非手术疗法治愈。175例随访3~24个(平均19.5)月,1例术后2个月发现阴道残端息肉,经手术切除治愈。　
结论：严格掌握联合手术指征,充分术前准备,多科室良好配合,腹腔镜联合手术能够有效地同时处理外科和妇科并存疾病,在基层医院具有良好的应用前景。