Femoral component fixation with and without intramedullary plug A 6-year follow-up

A total of 113 patients underwent a cemented total hip replacement (THR) operation involving femoral component fixation either without the use of a distal intramedullary plug (n = 57, group 1) or with the plug (n =56, group 2). We studied the femoral component fixation radiographically at on average 6 years after THR. The cement coating was assessed as technically good in 86% and 95% of groups 1 and 2, respectively. There was radiographically diagnosable loosening of the femoral component at the follow-up in 25 cases in which stems were inserted without the intramedullary plug, and in 6 cases in those with the plug (P < 0.0008), and the mean subsidence of the femoral component was 5 mm in group 1 and 1.5 mm (P < 0.0003) in group 2, respectively. Osteolytic changes around the femoral component were noticed in both groups in equal numbers and with no statistical difference. The use of a distal intramedullary plug in the cementation of the femoral stem results in a better cement coating, reduces femoral component subsidence and ameliorates the loosening rates.     

Follow up of growth and steroids in premature adrenarche

In a follow up study of 34 patients with premature adrenarche we examined serum adrenal androgen levels and growth. The majority (28/34) showed an upward bend in the growth curve which, at the mean age of 2.3 years, preceded other signs of adrenarche on average by 3.8 years. Pubertal growth spurt was missing or reduced in 50% of the patients (8/16), however, final height did not differ from that expected from parental heights. Adrenal androgens did not remain elevated at adolescence. The mean age at menarche for all the girls was 0.5 years younger than in the general population.Conclusion Our findings imply that premature adrenarche may start earlier than previously recognized. Compared to ordinary growth these children seen to use a greater part of their potential for adult height already at that early age.     

Ultrasonically activated shears in thyroidectomies: a randomized trial

OBJECTIVE: To test whether the advantages of the ultrasonically activated shears (UAS) observed in thyroidectomies in a previous matched-pair study could be repeated in a randomized trial. SUMMARY BACKGROUND DATA: The UAS has been documented, mainly in nonrandomized studies, to be a safe and fast device in video-assisted and conventional surgery. METHODS: Thyroidectomies and lobectomies performed for benign or malignant thyroid disease between August 1997 and January 1999 were included in this series. Separate randomization, resulting in four sets of envelopes, was done for one consultant endocrine surgeon and for senior residents for both lobectomies and for total thyroidectomies. The operations performed with the UAS were compared with operations performed with the conventional method, using ligatures as the main hemostatic method. Main outcome measures were operating time, postoperative serum calcium level, palsy of the recurrent laryngeal nerve, and amount of intraoperative and postoperative bleeding. Possible bias that could have been caused by imbalance between treatment groups for surgeon experience was tested by two-way analysis of covariance. RESULTS: Thirty-six patients were randomized, 19 to the UAS and 17 to the conventional group. Mean operating time was 99.1 minutes in the UAS group and 134.9 minutes in the conventional group. The average savings in operating time with the UAS was thus 35.8 minutes. There was no difference in complications between the groups. The estimated savings in operating time would have been 1.66 times that observed in this study if the groups had been unbalanced with reference to surgeon experience. CONCLUSION: The UAS is a usable device in total thyroidectomies and lobectomies.     

Homocysteine as a risk factor for CVD mortality in men with other CVD risk factors: the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study

OBJECTIVE: Based on case-control and prospective studies elevated blood total homocysteine (tHcy) has been suggested to be an independent risk factor for cardiovascular diseases (CVD). The purpose of the study was to explore the joint effect of increased serum tHcy concentration and other risk factors on the risk of CVD mortality in middle-aged men without a history of heart disease or stroke. DESIGN: A prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. SETTING: Eastern Finland. Subjects. A total of 802 men aged 46-64 years, examined in 1991-93. MAIN OUTCOME MEASURES: CVD mortality event. RESULTS: The mean serum tHcy concentration was 10.8 micromol L(-1) (SD 3.3). During the average follow-up time of 10.8 years 50 men experienced a CVD death. The hazard rate ratio for CVD mortality was 1.80 (95% confidence interval: 1.02-3.19) in men in the highest serum tHcy third versus lower thirds after adjustment for cardiovascular risk factors. Furthermore, elevated serum tHcy concentration appeared to increase the risk of CVD death in men who smoke or who have high circulating concentrations of serum total or LDL cholesterol, apo-B apolipoprotein or plasma fibrinogen. CONCLUSION: We conclude that homocysteine may increase the risk of CVD mortality in middle-aged men from Eastern Finland, and it may especially increase the risk when present with other risk factors for CVD.     

Factors associated with higher oxytocin requirements in labor

Objective: To identify clinical characteristics associated with high maximum oxytocin doses in women who achieve complete cervical dilation.

Methods: A retrospective nested case-control study was performed within a cohort of all term women at a single center between 2004 and 2008 who reached the second stage of labor. Cases were defined as women who had a maximum oxytocin dose during labor >20?mu/min, while women in the control group had a maximum oxytocin dose during labor of ≤20?mu/min. Exclusion criteria included no oxytocin administration during labor, multiple gestations, major fetal anomalies, nonvertex presentation, and prior cesarean delivery. Multiple maternal, fetal, and labor factors were evaluated with univariable analysis and multivariable logistic regression.

Results: Maximum oxytocin doses >20?mu/min were administered to 108 women (3.6%), while 2864 women received doses ≤20?mu/min. Factors associated with higher maximum oxytocin dose after adjusting for relevant confounders included maternal diabetes, birthweight >4000?g, intrapartum fever, administration of magnesium, and induction of labor.

Conclusions: Few women who achieve complete cervical dilation require high doses of oxytocin. We identified maternal, fetal and labor factors that characterize this group of parturients.     

Functional genomics bridges the gap between quantitative genetics and molecular biology

Deep characterization of molecular function of genetic variants in the human genome is becoming increasingly important for understanding genetic associations to disease and for learning to read the regulatory code of the genome. In this paper, I discuss how recent advances in both quantitative genetics and molecular biology have contributed to understanding functional effects of genetic variants, lessons learned from eQTL studies, and future challenges in this field.Most of human genetics research falls under two main questions: What are the genetic origins of variation in human disease and other traits? How does the blueprint of the human genome function to give rise to a living individual? These questions have different historical roots—in quantitative or medical genetics and molecular biology, respectively—as well as different molecular and statistical methods, and thus for decades they have been largely distinct areas of research. However, a question of increasing importance for understanding the human genome lies at their intersection: What are the functional effects of genetic variants across the human genome?The study of the evolutionary origins of human genetic variation and its contribution to human disease and traits has its origins in quantitative, statistical, and population genetics. Advances in high-throughput genotyping and sequencing technologies during the past 10 years have led to tremendous progress in this field, with the HapMap and 1000 Genomes projects (The International HapMap Consortium et al. 2007; The 1000 Genomes Project Consortium 2012) creating the foundation for hundreds of genome-wide association studies (GWAS) and now also rare variant analyses in the context of both common and rare diseases (Bamshad et al. 2011; Lee et al. 2014). However, these maps of genetic associations to disease do not give us direct information of the function of these variants: how they perturb the biology of the genome, the cell, and eventually the organism to affect disease risk—or from a population genetics perspective, to affect different selective pressures. Without such understanding, the information from genetic association studies will yield little benefit to human health.On the other side, understanding the mechanistic function of the human genome—as well as genomes of other species—has always been one of the fundamental questions of molecular biology. During the past five years, the approach has become genome-wide via the development of diverse high-throughput sequencing assays, applied to multiple cell types. Projects such as ENCODE (The ENCODE Project Consortium 2012), the Epigenomics Roadmap (Roadmap Epigenomics Consortium 2015), and FANTOM (The FANTOM Consortium and the RIKEN PMI and CLST (DGT) 2014) have produced large catalogs of functional elements in the genome—or more accurately, some genomes, since naturally, there is no archetype of the human genome. These studies do not typically capture variation in genome function among individuals, and the contribution of genetic differences in variation between samples is often ignored in study design. Thus, while these resources are used to annotate the putative regulatory function of genetic variants, this is done via indirect inference rather than direct measurement of genetic contribution to human phenotype diversity at the cellular level.The need to bridge conventional quantitative genetics and functional or molecular genetics has now become widely acknowledged (Fig. 1). The concept is not new—medical genetics has a long history of characterizing cellular effects of disease-causing mutations. However, the development of genome-wide methods now allows systematic high-throughput analysis, which is eventually more cost-efficient and informative of generalizable patterns than laborious locus-specific characterization. High-throughput analysis, with scalable and robust molecular assays, careful statistical analysis, and deep biological interpretation, are essential to achieve the future goal of being able to accurately read the genetic code, i.e., predict functional and phenotypic effects of genetic variants.Open in a separate windowFigure 1.Intersections of fields analyzing genetic variation, molecular biology, and medicine. GWAS and EWAS stand for genome-wide and epigenome-wide association studies, respectively, and eQTL is an abbreviation of expression quantitative trait loci.