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.     

The validation of the Finnish Hospital Discharge Register and Causes of Death Register data on stroke diagnoses.

BACKGROUND AND PURPOSE: Administrative registers, like hospital discharge registers and causes of death registers are used for the monitoring of disease incidences and in the follow-up studies. Obtaining reliable results requires that the diagnoses in these registers are correct and the coverage of the registers is high. The purpose of this study was to evaluate the validity of the Finnish hospital discharge registers and causes of death registers stroke diagnoses against the population-based FINSTROKE register. METHODS: All first stroke events from the hospital discharge registers and causes of death registers from the areas covered by the FINSTROKE register were obtained for years 1993-1998 and linked to the FINSTROKE register. The sensitivity and positive predictive values were calculated. RESULTS: A total of 3633 stroke events, 767 fatal and 2866 non-fatal strokes, were included in the registers. The sensitivity for all first stroke events was 85%, for fatal strokes 86% and for non-fatal strokes 85%. The positive predictive values for all first strokes was 86%, for fatal strokes 92% and for non-fatal strokes 85%. The sensitivity as well as the positive predictive values for subarachnoid haemorrhage and intracerebral haemorrhage was higher than for cerebral infarctions. There were no marked differences in the sensitivity or positive predictive values between men and women. CONCLUSIONS: The sensitivity and the positive predictive values of the Finnish hospital discharge registers and causes of death registers are fairly good. Finnish administrative registers can be used for the monitoring of stroke incidence, but the number of cerebral infarctions should be interpreted with caution.     

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.     

Multi-locus analysis of HLA class II genes in DR2-positive IDDM haplotypes in Finland

Abstract: In this study we characterized the haplotypes found in IDDM patients that normally confer resistance to the disease in order to localize the polymorphisms relevant for the protection. We studied 15 DR2-positive subjects with IDDM for their DRB1, DRB5 and DQB1 genes using RFLP, polymerase chain reaction (PCR), oligonucleotide typing, and in some specific cases direct sequencing after allele-specific PCR. In addition we analyzed 39 DR2-positive, IDDM non-associated haplotypes representing those haplotypes that are not inherited to probands and hence are present only in healthy family members. The frequency of the DRB1*1501-DRB5*0101-DQB1*0602 haplotype was slightly decreased among diabetic patients (80% vs. 92%). In addition, two unconventional haplotypes DRB1*1501-DRB5*0101-DQB1*05031 and DRB1*1501-DRB5*0101-DQB1*0502 were found in patients with IDDM while all the control ones were conventional. The sequencing of the DQB1*0602 allele present in IDDM haplotypes showed no differences when compared to the controls. These results support the primary but not absolute role of DQ in the protection against IDDM. An additional role of factors centromeric to DQB1 gene was suggested by findings based on the biallelic TaqI RFLP polymorphism of the DQA2 gene. All DR2-DQB1*0602 IDDM haplotypes were associated with the 2.1-kb fragment while in the control group the 2.1-kb and 1.9-kb fragments were evenly distributed.     

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.