Primary prevention in a high-risk group: smoking habits in adolescents with homozygous alpha-1-antitrypsin deficiency (ATD)

The serious form of alpha-1-antitrypsin deficiency (ATD) Pi ZZ strongly predisposes the individual for pulmonary emphysema and premature death in adulthood, especially if exposed to tobacco smoking. General screening of all new-born children was conducted in Sweden during 1972–1974, the major purpose being to reduce exposure of the child to parental smoking while growing up and to prevent the child from starting to smoke. Sixty-one children with ATD neonatally identified through mass-screening, and their families, have been compared with a demographically matched control group regarding smoking habits, as studied through interviews and questionnaires on two occasions. When the children were 5–7 years old, the smoking rates among parents of the ATD children and especially among the ATD fathers exceeded smoking rates for controls. Thirteen years later no differences in parental smoking were found between the groups. At 18–20 years of age the ATD children reported smoking significantly less than the control children (p < 0.05). From the perspective of prevention, the goal of the neonatal screening to reduce the smoking rates among the parents of the ATD children was not attained, while it was achieved among the ATD children. The results indicate that a screening program with early detection of ATD effectively prevents adolescent children from starting to smoke. From ethical, medical and psychological points of view, a voluntary screening program for ATD in pre-adolescence is recommended.     

Clinical effectiveness and safety experience with efalizumab in the treatment of patients with moderate-to-severe plaque psoriasis in Taiwan: results of an open-label, single-arm pilot study

Background No clinical trial of efalizumab has been conducted in Asia. Objective To determine the efficacy and safety of efalizumab in Taiwanese patients with psoriasis. Methods This is an open‐label, single‐arm pilot study conducted at two centres. Patients were given 1 mg/kg efalizumab subcutaneously once a week for 12 weeks and were then followed up for a further 12 weeks. Results A total of 49 patients participated in the study. The median improvement in Psoriasis Area and Severity Index (PASI) during the treatment period was 19.6%, and a ≥ 50% improvement in PASI was seen in 20.4%. Rebound was seen in 17.8% of patients, and anti‐efalizumab antibodies were detected in 41% of patients. The most frequent adverse events were headache (34.7%), arthralgia/arthritis (28.6%), psoriasis events (new form/exacerbation; 26.5%) and pruritus (22.4%). Conclusions This small pilot study indicated that efalizumab was effective in improving psoriasis symptoms in Taiwanese patients, with no new safety issues identified.     

Vertebral bone density in children: effect of puberty

To determine changes in bone density during growth, trabecular vertebral density and an index of spinal cortical bone were measured with quantitative computed tomography in 101 children. The children were divided by age into three groups: prepubertal, indeterminate, and pubertal. Compared with prepubertal children, pubertal adolescents had significantly higher trabecular bone density and more compact bone in the spine (P less than .001). After controlling for puberty, vertebral bone density failed to correlate significantly with age, sex, weight, height, surface area, and body mass index. The results indicate that bone density increases markedly during puberty.     

Platelet-derived growth factor promotes human peripheral monocyte activation

Like in the polymorphonuclear leukocyte (PMN), the platelet-derived growth factor (PDGF) purified to homogeneity is capable of inducing monocyte activation responses as evaluated by generation of superoxide anion (O-.2) from membrane-associated oxidase system, release of granule enzymes, and enhanced cell adherence and cell aggregation. Superoxide anion release was maximized at 10 ng/mL PDGF and was comparable to that induced by 10(-7) mol/L formyl-methionyl-leucyl- phenylalanine. The potency of PDGF to induce this response in monocytes was of the same magnitude as that observed in PMNs. Similarly, lysozyme release and monocyte adherence were also increased in a dose-dependent manner and achieved maximal responses at 40 ng/mL concentration of PDGF. The PDGF concentration required to achieve maximal monocyte aggregation was two-fold (60 ng/mL) of that found for PMNs. In contrast to PMNs, a positive correlation (gamma = .93; P less than .01) was observed between the increases of PDGF concentration and beta- glucuronidase release. These findings indicate that PDGF can induce the full sequence of cell activation events in human monocytes similar to human PMNs.     

Assessment of the frequency and costs of posttransplantation hospitalizations in patients receiving tacrolimus versus cyclosporine

We assessed the frequency and costs of hospitalizations in patients receiving tacrolimus (FK506) compared with patients receiving cyclosporine A for immunosuppression during 1 year after kidney transplantation. Four hundred twelve cadaveric kidney transplant recipients were randomized onto a phase III, prospective, multicenter, clinical trial. Hospital billing data were collected for 1 year posttransplantation. Total inpatient costs were calculated from billed charges and standardized to 1995 US dollars. Medical resource utilization rates and inpatient costs were compared between treatment groups using unpaired Student's t-tests. Complete billing data (transplantation and all posttransplantation hospitalizations) were available for 65% (268 of 412) of the study patients. Among tacrolimus and cyclosporine patients with complete billing data, the rates of allograft rejection were 32% and 47%, respectively (P=0.009), and the rates of rehospitalization during the year after transplantation were 53% and 63%, respectively (P=0.080). The mean per-episode rehospitalization costs were significantly lower among tacrolimus-treated patients compared with cyclosporine-treated patients ($7,495 v $11,497; P=0.031), and the mean total rehospitalization costs were significantly lower in the tacrolimus group compared with the cyclosporine group ($8,550 v $14,869; P=0.029). In addition, the total 1-year hospitalization costs (including transplantation and posttransplantation hospitalizations) were significantly lower in the tacrolimus group compared with the cyclosporine group ($53,435 v $61,191; P=0.046). Compared with cyclosporine-based immunosuppression, tacrolimus-based immunosuppression for kidney transplant recipients was associated with a significantly lower rate of rejection, which was associated with significantly lower per-episode rehospitalization costs, lower total 1-year rehospitalization costs, and lower total 1-year hospitalization costs.     

纳米羟基磷灰石／壳聚糖复合人工骨的成骨及再血管化

目的:通过纳米羟基磷灰石/壳聚糖(N-HA/CS)复合骨形态发生蛋白(BMP)制备N-HA/CS-BMP复合人工骨,初步了解其植入后成骨与血管长入之间的关系,以及复合人工骨的孔径对再血管化的影响。方法:①材料的制备:采用共沉淀法、粒子沥滤法制备N-HA/CS多孔复合材料,孔隙率为85%,孔径为100￣500μm;通过N-HA/CS与氧化锌粉末按质量比为8∶1的方式混合制备成致密复合材料;然后分别复合BMP制备N-HA/CS-BMP复合人工骨。②实验过程:20只新西兰兔,在兔双后肢胫骨近段内侧用直径为3.5mm手摇钻头钻2个孔制备骨缺损模型。随机取15只兔,右侧植入2块多孔N-HA/CS-BMP复合人工骨为多孔N-HA/CS BMP组,左侧植入2块致密N-HA/CS-BMP复合人工骨为致密N-HA/CS BMP组;另5只兔右侧植入2块多孔N-HA/CS为多孔N-HA/CS组,左侧植入2块致密N-HA/CS为致密N-HA/CS组。③观察指标:术后4,6,8周麻醉后墨汁灌注处死动物取出标本,行大体观察、X射线检查、组织学观察、Ⅰ型胶原免疫组化染色、显微计算机图像采集分析,了解各组成骨能力、血管化程度、复合人工骨的成骨与血管化之间的相互关系。结果:①一般情况:术后死亡2只动物,2只一侧肢体发生骨折,伤口均于2周左右愈合,未发生感染。②X射线检查:术后4,6周显示植入孔明显,材料与骨之间有密度减低的透光环,8周材料与骨结合紧密,透光环消失。③组织学观察:术后4,6周的材料内的炎性反应较重,主要是白细胞和巨噬细胞,8周的材料内炎性反应减轻;8周壳聚糖大部分降解,从而显现出羟基磷灰石的多孔结构。④显微计算机图像分析:多孔N-HA/CS BMP组血管密度和新生骨小梁面积大于其他3组(P<0.05),多孔N-HA/CS BMP组血管密度与骨小梁面积呈直线正相关关系(r=0.483,P=0.003)。⑤Ⅰ型胶原免疫组织化学染色显示结果支持显微计算机图像分析结果。结论:复合人工骨的成骨与血管化呈直线正相关关系,复合人工骨的成骨与血管化在早期是随着材料降解而完成的,多孔结构在晚期对血管化和成骨有利。