Effect of impact exercise on bone mineral density in elderly women with low BMD: a population-based randomized controlled 30-month intervention

Evidence of the effect of exercise on bone loss comes mainly from studies in voluntary postmenopausal women, and no population-based, long-term interventions have been performed. The purpose of this population-based, randomized, controlled trial was to determine the effect of long-term impact exercise on bone mass at various skeletal sites in elderly women with low bone mineral density (BMD) at the radius and hip. Participants ( n =160) were randomly assigned to 30 months either of supervised and home-based impact exercise training or of no intervention. The primary outcome measures were femoral neck, trochanter and total hip BMD, and the secondary outcomes were bone density measures at the radius and calcaneum. Outcomes were assessed at baseline, 12 months and 30 months using blinded operators. The analyses were performed on an intention-to-treat analysis. Mean femoral neck and trochanter BMD decreased in the control group [–1.1%, 95% confidence interval (CI) –0.1% to –2.1% and –1.6%, 95% CI –0.4% to –2.7%], while no change occurred in the exercise group. Mean trochanter BMC decreased more in the control group (–7.7%, 95% CI –9.7% to –5.6% vs. –2.9%, 95% CI –5.3 to –0.9). There were six falls that resulted in fractures in the exercise group and 16 in the control group during the 30-month intervention ( P =0.019). A significant bone loss occurred in both groups at the radius and calcaneum. In multivariate analysis, weight gain was associated with increased BMD and BMC at all femur sites both in the exercise group and in the pooled groups. In conclusion, impact exercise had no effect on BMD, while there was a positive effect on BMC at the trochanter. Exercise may prevent fall-related fractures in elderly women with low bone mass.There was no conflict of interest.     

全膝关节置换翻修术的Meta分析

目的 通过对已报道的全膝关节置换翻修术文献进行总结分析,讨探膝关节置换翻修术前后的膝关节功能、翻修的主要原因、主要并发症及不同假体的术后疗效.方法 按照以下标准收集和分析有关全膝关节置换翻修术的文献:①1990年至2002年间发表,②报告患者数大于10例,③采用通用的膝关节评分标准.一名骨科专科医生独立收集数据,一名医学统计学专家独立采用Meta统计方法分析数据.结果 共有33 篇符合条件的文献被收集.患者共1356 例,其中男429例,女611例(部分文献性别分类数据缺失),平均年龄67岁(45～49岁),加权平均随访时间57个月( 6～108 个月),加权平均术前膝关节功能总评分为49 分(15～94分),术后为84分( 58～109分),全膝关节置换翻修术前后的总评分、功能评分、活动范围等有显著性提高,差异有统计学意义(总评分t=12.507,P<0.01, 功能评分t=4.704,P<0.01,活动范围:t=5.346,P< 0.01).全膝关节置换翻修术的原因主要是假体松动(55%),其它包括聚乙烯磨损(11%)、假体不稳(10%)、感染(7%).翻修术后的主要并发症仍然为假体松动(18%),其它包括假体不稳(16% )、感染(16% )、髌骨问题( 15% )及不明原因的膝关节疼痛(13%).髌骨问题包括髌骨脱位、半脱位、髌韧带撕裂、髌股关节疼痛等.结论 可以认为膝关节置换后翻修术是一种安全有效的手术.假体松动是膝关节置换翻新的主要原因和并发症.     

Current perspectives on HER2 testing: a review of national testing guidelines.

Knowledge of HER2 status is a prerequisite when considering a patient's eligibility for Herceptin (trastuzumab) therapy. Accurate assessment of HER2 status is essential to ensure that all patients who may benefit from Herceptin are correctly identified. There are several assays available to determine HER2 status: the most common in routine clinical practice are immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Various factors can affect the results achieved with these assays, including the assay antibody/probe, the methodology and the experience of personnel. Many countries have implemented national testing guidelines in an attempt to standardize testing procedures and make results more accurate. These guidelines vary in the level of detail and the number of recommendations. This review looks at areas of consensus between the different national testing guidelines and highlights where errors may arise during the testing procedure. The key point underlined by this review is that whatever method is used to test for HER2 status, the technology must be validated first, and there must be regular internal and external quality control and quality assurance procedures.     

Characterization of a novel breast carcinoma xenograft and cell line derived from a BRCA1 germ-line mutation carrier

A human tumor xenograft (L56Br-X1) was established from a breast cancer axillary lymph node metastasis of a 53-year-old woman with a BRCA1 germ-line nonsense mutation (1806C>T; Q563X), and a cell line (L56Br-C1) was subsequently derived from the xenograft. The xenograft carries only the mutant BRCA1 allele and expresses mutant BRCA1 mRNA but no BRCA1 protein as determined by immunoprecipitation or Western blotting. The primary tumor, lymph node metastasis, and xenograft were hypodiploid by DNA flow cytometry, whereas the cell line displayed an aneuploidy apparently developed via polyploidization. Cytogenetic analysis, spectral karyotyping, and comparative genomic hybridization of the cell line revealed a highly complex karyotype with numerous unbalanced translocations. The xenograft and cell line had retained a somatic TP53 missense mutation (S215I) originating from the primary tumors, as well as a lack of immunohistochemically detectable expression of steroid hormone receptors, epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER-2), and keratin 8. Global gene expression analysis by cDNA microarrays supported a correlation between the expression profiles of the primary tumor, lymph node metastasis, xenograft, and cell line. We conclude that L56Br-X1 and L56Br-C1 are useful model systems for studies of the pathogenesis and new therapeutic modalities of BRCA1-induced human breast cancer.     

Effect of porosity on the osteointegration and bone ingrowth of a weight-bearing nickel-titanium bone graft substitute

Porous nickel-titanium (NiTi) alloy is a promising new material for a bone graft substitute with good strength properties and an elastic modulus closer to that of bone than any other metallic material. The purpose of this study was to evaluate the effect of porosity on the osteointegration of NiTi implants in rat bone. The porosities (average void volume) and the mean pore size (MPS) were 66.1% and 259+/-30 microm (group 1, n=14), 59.2% and 272+/-17 microm (group 2, n=4) and 46.6% and 505+/-136 microm (group 3, n=15), respectively. The implants were implanted in the distal femoral metaphysis of the rats for 30 weeks. The proportional bone-implant contact was best in group 1 (51%) without a significant difference compared to group 3 (39%). Group 2 had lower contact values (29%) than group 1 (p=0.038). Fibrotic tissue within the porous implant was found more often in group 1 than in group 3 (p=0.021), in which 12 samples out of 15 showed no signs of fibrosis. In conclusion, porosity of 66.1% (MPS 259+/-30 microm) showed best bone contact (51%) of the porosities tested here. However, the porosity of 46.6% (MPS 505+/-136 microm) with bone contact of 39% was not significantly inferior in this respect and showed lower incidence of fibrosis within the porous implant.     

Estimation of genetic risk for type 1 diabetes

The most important gene loci defining risk of type 1 diabetes mellitus (T1DM) are located within the HLA gene region. HLA-DQ molecules are of primary importance but HLA-DR gene products modify the risk conferred by HLA-DQ. The risk associated with an HLA genotype is defined by the particular combination of susceptible and protective alleles. The highest risk is associated with a combination of two different risk haplotypes (7% risk to develop T1DM in Finland) whereas protective genotypes covering 69% of population have a risk of less than 0.2%). The complicated analysis of HLA genotypes is simplified by strong linkage disequilibrium between HLA-DRB1, -DQA1 and -DQB1 loci. In many cases one can deduce the alleles of other loci based on determination of the alleles in one locus. Differences between various populations in the frequency of marker alleles and in the linkages between them has to be taken into account. We have developed PCR based typing methods that utilize blood spot samples, microtiter plate format and lanthanide labeled oligonucleotide probes to define HLA-DQ and -DR alleles relevant for T1DM risk. Typing is run stepwise so that after initial HLA-DQB1 typing only those samples will be further analyzed in which -DQA1 or -DRB1 typing is informative and expected to contribute to the risk estimation. This method has been used to screen more than 50,000 newborn infants in Finland over a time period of 6 years, and it has been able to identify most children who have developed T1D during the follow-up period. The efficiency of the procedure has also been tested in Finnish and Greek populations.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Haplotype analysis in gelsoiin-related amyloidosis reveals independent origin of identical mutation (G654A) of gelsolin in Finland and Japan

Familial amyloidosis, Finnish type (FAF) (gelsolin-related amyloidosis) is an autosomal dominant form of systemic amyloidosis characterized by corneal lattice dystrophy and peripheral polyneuropathy. The accumulating protein in FAF consists of fragments of gelsolin, an actin-modulating protein. The gelsolin mutation G654A has been found in both Finnish and Japanese patients. To study the origin of the gelsolin mutation in these patients we performed haplotype analysis in 10 Finnish and 2 Japanese FAF families. Poymorphic DNA markers GSN, D9S103, AFMa061xd9, and AFMa139xb9 revealed a uniform disease haplotype in all the disease-associated chromosomes of the Finnish FAF families, which was different from the one observed in the Japanese families. The present results and the previously detected gelsolin mutation G654T in Czech and Danish FAF patients suggest that nucle otide 654 may represent a mutation hot spot in the gelsolin gene. The DNA markers studied here will be useful in future genealogical analyses of FAF. © 1995 Wiley-Liss, Inc.