The hematopoietic stem cell antigen, CD34, is not expressed on the malignant cells in multiple myeloma

Autologous stem cell transplantation has become an important therapy in multiple myeloma (MM). To develop adequate autograft purging methods, it is necessary to determine whether antigens expressed on early hematopoietic progenitors exist on malignant cells. The Ig heavy chain produced by the MM cells shows evidence of prior somatic mutation without intraclonal diversity. As a result, this sequence can be used as a specific marker to detect all members of the malignant clone. The Ig heavy chain sequence expressed by the MM cells was obtained in five patients with advanced disease. Patient specific oligonucleotide primers were designed based on the complementarity determining regions (CDR) of each MM Ig sequence and used to amplify DNA by polymerase chain reaction for the detection of malignant cells. A highly purified collection of CD34+ cells was obtained after passage of the initial bone marrow cells through an immunoadsorption column and fluorescence- activated cell sorting. Despite an assay sensitivity of 1 tumor cell in 2,500 to 44,000 normal cells, none of the CD34+ samples showed product with the myeloma-specific CDR primers. Therefore, positive selection for cells bearing this antigen should yield a tumor-free autograft capable of providing hematopoietic recovery after myeloablative chemotherapy.     

Transplantation of CD34+ peripheral blood progenitor cells after high- dose chemotherapy for patients with advanced multiple myeloma

A major potential problem of autologous transplantation in the treatment of advanced malignancy is the infusion of tumor cells. A multi-institutional study of purified CD34-selected peripheral blood progenitor cell (PBPC) transplantation was conducted in 37 patients with advanced multiple myeloma receiving myeloablative chemotherapy. Fourteen days after intermediate-dose cyclophosphamide, prednisone, and granulocyte colony-stimulating factor (G-CSF), a median of 3 (range, 2 to 5) 10-L leukaphereses yielded 9.8 x 10(8)/kg (range, 3.7 to 28.3) mononuclear cells. The adsorbed (column-bound) fraction contained 5.9 x 10(6) cells/kg (range, 1.6 to 25.5) with 4.65 x 10(6) CD34 cells/kg (range, 1.2 to 23.3). Using Poisson distribution analysis of positive polymerase chain reactions with patient-specific complementarity- determining region 1 (CDR1) and CDR3 Ig-gene primers, tumor was detected in leukapheresis products from 8 to 14 unselected patients and ranged from 1.13 x 10(4) to 2.14 x 10(6) malignant cells/kg. After CD34 selection, residual tumor was detected in only three patients' products. Overall, a greater than 2.7- to 4.5-log reduction in contaminating multiple myeloma cells was achieved. CD34 PBPCs were infused 1 day after busulfan (14 mg/kg) and cyclophosphamide (120 mg/kg), and granulocyte-macrophage colony-stimulating factor was used until hematologic recovery. The median time to both neutrophil and platelet recovery was 12 days (range, 11 to 16 days and 9 to 52 days, respectively). The median number of erythrocyte and platelet transfusions was 7 (range, 2 to 37) and 3 (range, 0 to 85), respectively. Patients receiving fewer than 2 x 10(6) CD34 cells/kg had significantly prolonged neutropenia, thrombocytopenia, and an increased red blood cell and platelet transfusion requirement. Thus, CD34 selection of PBPCs markedly reduces tumor contamination in multiple myeloma and provides effective hematopoietic support for patients receiving myeloablative therapy.     

Human embryonic somatomedin.

A radioreceptor assay utilizing human fetal brain plasma membrane as matrix and somatomedin A as ligand (fetal brain RRA-SMA) was developed. Increased levels of fetal brain RRA-SMA were found in the fetal circulation. The concentration was approximately 4-fold higher in the fetal as compared to the adult human. At birth, values fell within the adult range. In contrast, adult somatomedins determined by somatomedin radioimmunoassay were undetectable in the fetus and below the adult range at birth. Levels of fetal brain RRA-SMA were decreased in fetuses with different clinical disorders. In healthy newborns at cesarean section a significant correlation between serum fetal brain RRA-SMA values and birth weight and length was found. These results indicate the presence of an embryonic somatomedin in humans. The fetal brain RRA-SMA may provide a reliable index of fetal growth.     

The influence of cigarette smoking on antenatal growth, birth size, and the insulin-like growth factor axis

BACKGROUND: Maternal smoking during pregnancy is associated with a reduction in birth size. Very few studies have collated changes in fetal biometry, neonatal anthropometry, biochemical factors involved in fetal growth, and measures of uterine and umbilical blood flow. METHODS: We related smoking status in 1650 low-risk, singleton Caucasian pregnancies delivering at term to measures of fetal growth, uterine and umbilical artery blood flow, placental appearance, birth size, and cord concentrations of IGF-I and -II and IGF binding protein (IGFBP)-3. RESULTS: Mothers who smoked in pregnancy were younger (P < 0.001) and shorter (P = 0.03) and from lower socioeconomic groups (P < 0.001). Mean umbilical artery blood flow at 20 wk gestation was not associated with smoking status but was significantly higher in smokers at 30 wk (P = 0.006). Uterine artery blood flow was unaffected. Smoking was associated with an increase in the percentage of abnormal placentas in a dose-dependent manner and with a 3.1-fold increased risk (odds ratio 3.1, 95% confidence interval 1.3-7.6) of abnormal umbilical artery blood flow (P = 0.009). Smoking was associated with a reduction in fetal femur length (P = 0.005) and abdominal circumference as well as birth weight, length, and head circumference but not skinfold thickness. Cord plasma concentrations of IGF-I and IGFBP-3 were lower in the babies of mothers who had smoked (P = 0.02 and P = 0.01, respectively). CONCLUSION: We concluded that maternal smoking is associated with an altered placental appearance on ultrasonography, increased umbilical artery blood flow resistance, and a reduction in longitudinal and intraabdominal organ growth. Circulating concentrations of IGF-I and IGFBP-3 along with measures of birth size but not markers of body fat are reduced, suggesting smoking results in a reduction in organ size and function.     

Identifying and characterizing casein kinase II in human platelets

We have recently shown that inhibition of protein phosphatases in platelets causes increases in protein phosphorylations with a concomitant inhibition of platelet responses. The burst in protein phosphorylation appears to be catalyzed by messenger-independent protein kinases. The aim of the present study was to characterize the presence of broad families of protein kinases found in platelets. Lysates of control and thrombin-stimulated platelets were prepared, and proteins were separated on MONO Q fast protein liquid chromatography. In addition to the presence of histone protein kinase and tyrosine kinase activities, human platelets contain casein kinase II (CKII) activity as assessed by phosphorylation of a specific substrate peptide. Western blot analysis and immunogold electron microscopy studies further showed the presence of alpha-, alpha'-, and beta- subunits of CKII. The enzyme appears to be distributed throughout the cytosol and not secreted after thrombin treatment. Immunoprecipitation studies suggest that at least some of the holoenzymes exist as an alpha alpha' beta 2 complex. Although no activation of the enzyme was detected after thrombin treatment, our results show that CKII is a major messenger-independent protein kinase in platelets.     

Effects of rheumatoid arthritis on employment and social participation during the first years of disease in The Netherlands

OBJECTIVE: To study the effect of rheumatoid arthritis (RA) on working capabilities and social participation, including non-paying jobs, during the first 6 yr of disease. DESIGN: Cross-sectional study. METHODS: In April 1996, a self-reporting questionnaire was sent to 424 participants of a population-based clinical trial of therapeutic strategies for early RA initiated in 1990. RESULTS: A total of 363 completed questionnaires were returned (response = 86%). Disease duration varied from < 1 to 6 yr (mean 2.8 yr). The employment rate was low in the RA population compared to the Dutch population. In the male 45- to 64-yr-old group, 63% of RA patients were not employed compared to 32% of the Dutch population (P < 0.01). In the female 45- to 64-yr- old group, 76% of the RA population vs 67% of the Dutch were not employed (P < 0.05). Of the employed patients, 59% reported that RA affected their working capabilities, e.g. they worked an average of 21 h per week less due to RA. Of the patients without a paying job, 41% believed that this was (partly) due to RA. In addition, fewer RA patients had non-paying jobs and they performed fewer household activities compared to the general Dutch population. CONCLUSION: RA already has a negative influence on the working capabilities, social participation and household activities of these patients during the first 6 yr of disease.      

Risk factors for coronary artery disease: a study comparing hypercholesterolaemia and hypertriglyceridaemia in angiographically characterized patients

Fifty-two male patients undergoing coronary angiography were allocated to four groups each consisting of 13 subjects: group I had normal coronary arteries and patients in groups II-IV exhibited coronary artery disease. In group II, plasma cholesterol was below 250 mg dl-1 and triglycerides below 160 mg dl-1; in group III, cholesterol was above 270 mg dl-1 and triglycerides under 160 mg dl-1; and in group IV, cholesterol was under 270 mg dl-1 and triglycerides above 180 mg dl-1. The hypertriglyceridaemic group IV had the highest coronary score. In addition, it had lowest lipoprotein lipase activity, lowest HDL-cholesterol and lowest high-density lipoproteins-2 (HDL-2) levels, suggesting that this type of hypertriglyceridaemia is caused--at least in part--by lipoprotein lipase deficiency with impaired removal of the triglyceride-rich lipoproteins and increased catabolism of HDL-2. Our findings point towards a type of hypertriglyceridaemia strongly associated with coronary artery disease which should therefore be treated accordingly.     

人工髓核假体置换治疗腰椎间盘突出症29例：13例随访术后4年假体移位发生率

目的:评价人工髓核假体置换治疗腰椎间盘突出症的临床效果。方法:①2002-01/2004-04在中山大学附属第二医院对29例腰椎间盘突出症患者进行人工髓核置换术治疗。其中单节段L4,5者26例,双节段L4,5及L5S1者3例。所有患者经严格非手术治疗无效、无法坚持正常的日常生活和工作并经手术签字同意。②采取三种手术入路:单节段病变中,24例经后侧入路,2例经腰大肌的前外侧入路,均行单枚人工髓核植入;双节段3例则采用前路腹膜外入路,L4,5进行人工椎间盘置换术,L5S1行单枚人工髓核植入。人工髓核为美国Raymedica公司生产的假体,其外套为聚乙烯纤维,核心为能吸水膨胀的半流动性水凝胶(聚丙烯-聚丙烯酰胺共聚物)。③随访方法:分别在术后第6周、3个月、6个月、1年、2年、3年及4年对患者进行随访。随访观察内容包括10分制的视觉模拟疼痛评分,Oswestry疼痛功能指数评分,Prolo腰椎术后功能评分以及根据Macnab标准进行临床疗效评价。结果:术后第6周、3个月、6个月全部获得随访,术后1年27例获得随访,术后2年24例获得随访,术后3年18例获得随访,术后4年13例获得随访。①临床疗效:优10例(34.5%),良16例(55.2%),差(发生假体移位突出)3例(10.4%),优良率达89.7%。②Oswestry功能障碍指数评分:术前平均为(59.0±5.6)%,术后6周(50.0±4.3)%,3个月(35.2±3.8)%,6个月(23.0±1.7)%,1年(17.4±1.4)%,2年(11.8±0.9)%,3年(10.3±1.1)%,4年为(9.8±0.7)%。视觉模拟疼痛评分:术前平均为(8.0±1.2)分,术后6周(4.5±0.7)分,3个月(3.2±0.6)分,6个月(3.0±0.7)分,1年后则降为(2.8±0.5)分,2年(2.5±0.6)分,3年(2.2±0.4)分,4年(2.0±0.3)分。Prolo腰椎术后功能评分:术前平均为(4.4±0.5)分,术后6周(5.3±0.7)分,3个月(6.5±1.1)分,6个月(7.1±0.8)分,术后1年则为(8.5±1.2)分,2年(8.8±0.9)分,3年为(9.0±1.2)分,4年(9.1±0.7)分;手术前后比较,差异均有显著性(P<0.001)。③并发症:术后早期有2例假体移位而再次手术,1例于术后3年发生假体移位突出,但无症状,无需再次手术。结论:人工髓核置换术治疗腰椎间盘突出症效果较好,能够恢复腰椎节段的稳定性和活动度,减轻或消除腰腿痛的症状。     

The impact of a specific aqua-training for adult haemophilic patients - results of the WATERCISE study (WAT-QoL)

Summary. Sport is increasingly recommended for haemophilic patients due to physical and psychological benefits. ‘WATERCISE’ is a specific aqua‐training programme for haemophiliacs in which endurance, strength, coordination and mobility are trained. In the WAT‐QoL study benefits and risks of regular WATERCISE training sessions were investigated in terms of health‐related quality of life (HRQoL), physical functioning (PF), orthopaedic joint status (OJS), bleeding frequency and factor consumption. Patients in the WATERCISE group attended an aqua‐training programme once a week for 1 h over 12 months, patients in the control group did not. Patients were matched for clinical and demographic data. Information on clinical data, orthopaedic status, PF (HEP‐Test‐Q) and HRQoL were collected in both groups at baseline and at follow‐up (6 and 12 months). Twenty‐eight adult severely affected haemophilic patients (WATERCISE group: 10 haemophilia A (HA), 3 haemophilia B (HB) patients; control group: 12 HA and 3 HB patients) were enrolled (aged 40.68 ± 12.7 years). Baseline data (body mass indices, OJS, sportive activities, HRQoL and PF) were well distributed between groups. After 12 months the WATERCISE group reported a significantly better PF (M_W = 65.22, SD = 11.3; M_C = 52.5, SD = 15.0), especially for endurance (P < 0.004). Although always differently reported by the patients within the WATERCISE group, HRQoL did not prove to be significantly different between groups. WATERCISE seems to have a positive effect on the PF of patients suffering from haemophilia. These study findings need to be further investigated in a larger study group.