Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group

BACKGROUND: Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known. METHODS: We studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [-4] or lower than -3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than -4 or lower than -3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture. RESULTS: Overall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned to placebo (relative risk, 0.7; 95 percent confidence interval, 0.6 to 0.9; P=0.02). In the group of women with osteoporosis (those 70 to 79 years old), the incidence of hip fracture among those assigned to risedronate was 1.9 percent, as compared with 3.2 percent among those assigned to placebo (relative risk, 0.6; 95 percent confidence interval, 0.4 to 0.9; P=0.009). In the group of women selected primarily on the basis of nonskeletal risk factors (those at least 80 years of age), the incidence of hip fracture was 4.2 percent among those assigned to risedronate and 5.1 percent among those assigned to placebo (P=0.35). CONCLUSIONS: Risedronate significantly reduces the risk of hip fracture among elderly women with confirmed osteoporosis but not among elderly women selected primarily on the basis of risk factors other than low bone mineral density.     

Differential expression of TGF-beta1 and TGF-beta3 in serosal tissues of human intraperitoneal organs and peritoneal adhesions

Elevated local expression of transforming growth factor (TGF-beta) has been associated with increased incidence of peritoneal adhesion formation. In this study we determine whether differences in basal expression of TGF-beta in serosal tissue of peritoneal organs correlate with incidence of adhesion formation. Serosal tissue of parietal peritoneum, uterus, oviduct, ovary, omentum, large and small bowels as well as adhesions, skin, fascia, subcutaneous tissue, peritoneal fluid and serum were collected from 57 subjects with/without adhesions who were undergoing abdominal/pelvic surgery. To determine TGF-beta1 and TGF-beta3 mRNA and protein expression, total RNA and protein were isolated from these tissues and along with the fluids, subjected to quantitative RT-PCR and enzyme-linked immunosorbent assay (ELISA) respectively. Tissue sections were immunostained for TGF-beta1 and TGF-beta3 protein. We found that TGF-beta1 and TGF-beta3 mRNA and protein are expressed in these tissues and present in peritoneal fluids and serum, with considerable variations in level of their expression. Comparatively, there was more variation in TGF-beta1 than TGF-beta3 expression without age or gender relation. Adhesions express a significantly higher TGF-beta1 mRNA and have the highest TGF-beta1:TGF-beta3 ratio, with lowest concentrations and ratio detected in omentum, small and large bowels; in contrast uterus expresses higher TGF-beta3, with lowest concentrations detected in subcutaneous tissue and large bowels (P < 0.05). A similar trend was also observed for total (active + latent) TGF-beta1 protein expression, with low active TGF-beta1 that was not significantly different among the tissue extracts and fluids. However, the lowest active:total TGF-beta1 ratio was found in adhesions and ovary. In subjects with adhesions, the adhesions express significantly more TGF-beta1 compared to parietal peritoneum (P < 0.05). Immunoreactive TGF-beta1 and TGF-beta3 protein were present in various cell types in these tissues with intensity reflecting their mRNA and protein expression. In conclusion, we provided evidence that serosal tissue of various peritoneal organs and adhesions express TGF-beta1 and TGF-beta3. Since TGF-beta is expressed differently in these tissues and tissue injury often alters the expression of TGF-beta, we propose that tissues with a higher basal expression of TGF-beta may become predisposed to develop more adhesions compared to others.     

Microtubule turnover in ooplasm biopsy reflects ageing phenomena in the parent oocyte

Oviductal oocytes retrieved from superovulated B6D2F1 mice at 13.5, 16 and 19 h after human chorionic gonadotrophin (HCG) (groups A, B and C respectively, n = 382) were micromanipulated to obtain 12-20 mum sized ooplasm biopsy fragments. Experiments were divided into three sets. Ooplasmic microtubule dynamics were studied in ooplasm biopsy specimens and parent oocytes (set 1) and ooplasm biopsy specimens (set 2), whilst zona pellucida dissolution time, cortical granule loss and spindle/chromatin morphology using confocal microscopy were also studied in parent oocytes (set 2). Oocytes withstood oocyte biopsy with a high survival rate (98.2%) and the biopsied oocytes underwent successful fertilization and development (set 3). An absolute one-to-one correlation was seen between the oocyte biopsy specimens and the parent oocytes in terms of ooplasmic microtubule dynamics (set 1), and increased ooplasmic microtubule dynamics in oocyte biopsy specimens paralleled ageing phenomena in the parent oocytes (set 2). Zona pellucida dissolution time was significantly lower in parent oocytes from group A versus groups B (P = 0.032), and C (P < 0.001). (Groups A, B, C include minimal, moderate, increased ooplasmic microtubule dynamics in oocyte biopsy specimens respectively.) Oocyte cortical granule loss and spindle/chromatin abnormalities were mainly seen in group C (P < 0.001). Oocyte biopsy can thus be applied to judge age-related changes in the parent oocytes.     

TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons

Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3^–/– mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell–derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity.     

B超引导下臂丛神经阻滞麻醉的效果及安全性

目的研究B超引导下臂丛神经阻滞麻醉的临床效果及安全性。方法将本院行上肢手术的90例患者随机分为对照组(n=48)和B超引导组(n=42)。对照组以盲探的方法行臂丛神经阻滞麻醉,B超引导组在B型超声仪引导下行臂丛神经阻滞麻醉。比较两组的麻醉效果。结果B超引导组感觉阻滞起效时间、麻醉药物使用剂量均优于对照组,但麻醉操作时间长于对照组(P<0.05)。B超引导组不同臂丛神经的感觉阻滞完善率均高于对照组,并发症总发生率低于对照组(P<0.05)。结论与盲探法相比,B超引导下行臂丛神经阻滞麻醉的麻醉操作时间虽然有所延长,然而麻醉效果佳,能够缩短感觉阻滞起效时间、减少麻醉药物用量,且安全性好。     

瑞芬太尼静脉自控镇痛在分娩镇痛中的应用效果及对产妇皮质醇和去甲肾上腺素水平的影响

目的探讨瑞芬太尼患者静脉自控镇痛(PCIA)在分娩镇痛中的应用效果及对产妇血清皮质醇(Cor)、去肾上腺素(NE)水平的影响。方法将足月待产的284例产妇随机分为A组(142例,瑞芬太尼PCIA)和B组[142例,罗哌卡因联合舒芬太尼患者硬膜外自控镇痛(PCEA)]。同时,选择同期在我院进行分娩的150例不要求镇痛的产妇作为C组。比较三组产妇的分娩镇痛效果及血清Cor、NE水平。结果镇痛后10、20 min及宫口全开时,A、B组的VAS评分低于镇痛前及C组(P<0.05),而A、B组镇痛后10、20 min的VAS评分无显著差异(P>0.05)。A组第一、二产程时间短于B、C组,C组短于B组(P<0.05)。三组新生儿Apgar评分比较,差异无统计学意义(P>0.05)。A、B组药物相关不良反应总发生率无显著差异(P>0.05)。分娩后30 min,A、B组的血清NE、Cor水平低于分娩前及C组,A组低于B组(P<0.05),C组则无明显变化(P>0.05)。结论本研究的两种镇痛方式用于产妇分娩镇痛中均可减轻产妇的疼痛程度,且镇痛效果相当、对产妇和新生儿均无不良影响,但瑞芬太尼PCIA可有效缩短产程,降低血清Cor、NE水平,是一种安全有效的分娩镇痛模式。     

自体外周血造血干细胞联合自体骨髓移植治疗难治性淋巴瘤的临床分析

本研究通过回顾性分析自体外周造血干细胞移植、自体骨髓移植及二者联合移植在治疗难治性恶性淋巴瘤的疗效、毒副作用、造血和免疫功能恢复速度等临床方面的差异,总结归纳三种不同移植方式在治疗难治性淋巴瘤方面的优劣。68例难治性恶性淋巴瘤患者接受了大剂量放化疗结合自体造血干细胞移植治疗,其中10例患者为单一自体骨髓移植（autologous bone marrow transplantation,ABMT）,46例患者为单一自体外周血造血干细胞移植（autologous peripheral blood hematopoietic stem cell transplantation,APBHSCT）,12例患者为自体外周血造血干细胞联合自体骨髓移植（autologous peripheral blood hematopoietic stem cells transplantation combined with autologous bone marrow transplantation,APBHSCT＋ABMT）。结果表明：ABMT、APBHSCT、APBHSCT＋ABMT的治疗有效率和1、3、5年生存率分别为（90％和75％、57．1％、33．3％）;（86．4％和74．4％、54．2％、38．1％）;（83．3％和72．7％、55．6％、40％）。白细胞恢复时间分别为13天、11天、8天,血小板恢复时间分别为17天、14天、9天。在移植后3个月、6个月、1年时检测ABMT、APBHSCT、APBHSCT＋ABMT患者T细胞亚群正常率分别为（0％、33．3％、60％）,（10．8％、32％、73．9％）,（27．3％、55．6％、85．7％）。结论：自体外周血造血干细胞联合自体骨髓移植与单一自体外周造血干细胞移植治疗难治性恶性淋巴瘤的临床疗效和毒副作用当,但联合造血干细胞移植（APBHSCT＋ABMT）患者的造血功能恢复略快,有利于拓宽年龄偏大和造血功能受损患者移植方式的选择。     

双色双融合荧光原位杂交探针检测慢性髓系白血病Bcr/Abl基因重排的研究

本研究探讨双色双融合荧光原位杂交技术(DC-DF-FISH)在慢性髓系白血病(CML)中的应用价值,应用常规R-显带技术、DC-DF-FISH、RT-PCR技术检测41例CML患者的染色体核型及bcr/abl融合基因.结果表明,对于初诊CML的18例患者,R-显带显示Ph染色体阳性检出率为94.4%(17/18),DC-DF-FISH阳性检出率也为94.4%(17/18),对于治疗后CML的18例患者,R-显带显示14例有可分析分裂相,其中有11例存在Ph染色体,阳性检出率为78.6%(11/14);而用DC-DF-FISH检测治疗后患者的阳性率为94.4%(17/18);移植后的5例患者R-显带均未检出Ph染色体,而FISH检测出1例bcr/abl基因阳性,RT-PCR证实了FISH的检测结论,但在移植患者中,RT-PCR无阳性发现.结论:双色双融合荧光原位杂交技术具有高度的准确性、可靠性,是检测CML患者bcr/abl基因重排的可靠方法,适用于CML的诊断、疗效判定及微小残留病灶的检测.     

Prolactin as a modulator of B cell function: implications for SLE.

Prolactin is not only a lactigenic hormone but also an immunomodulator involved in lymphocyte survival, activation and proliferation. There is increasing data implicating prolactin in autoimmunity, and specifically in SLE. Increased serum prolactin levels have been reported in lupus patients of both genders, and have been associated with accelerated disease expression and early mortality in lupus-prone mice. Furthermore, suppression of prolactin secretion with bromocriptine provides beneficial effects in murine lupus, and perhaps in some SLE patients as well. Treatment with prolactin that causes mild to moderate hyperprolactinemia, similar to that present in SLE patients, breaks tolerance and induces a lupus-like illness in non-spontaneously autoimmune mice with a susceptible genetic background. These immuno stimulatory effects of prolactin are mediated by a decrease in negative selection and the maturation of autoreactive B cells to the follicular subset. Consistent with the fact that follicular B cells are T cell dependent, CD4+ T cells are necessary for the prolactin-mediated break down of B cell tolerance. In mice, the effects of prolactin on the immune system are genetically determined, suggesting that only a subset of SLE patients are likely to have a prolactin-responsive disease. The manipulation of serum prolactin or, even more specifically, follicular B cells that are susceptible to the immuno stimulatory effects of prolactin, may provide novel therapeutic options for those SLE patients with a prolactin-modulated disease.