牛津单髁膝关节置换：长期结果

牛津膝置换是使用最广泛的膝关节单髁置换（UKR）。牛津膝在37年前开始应用,拥有一个全匹配的活动衬垫,因而磨损率非常低。牛津膝最主要的使用指征是膝关节前内侧骨关节炎,这种病人至少占所有需要行膝关节置换术患者的50％。由于这一系统的设计特点,传统UKR的反指征,如年龄、活动量、肥胖、髌股关节损害和软骨钙质沉着症等对于牛津膝均不是反指征。与全膝关节置换（TKR）相比,牛津膝提供更快的康复、更好的功能、更大的活动度和更好的术后满意度,发生并发症更少、程度更轻,病残率和死亡率更低。一个持续超过30年的研究显示在90％的病例中,牛津膝为患者终生提供了优或良的临床结果,且不需要翻修。在最近15年,牛津膝通过微创手术入路植入,涉及6000多例使用该入路牛津膝置换的9个研究报道显示,10年生存率约95％。在许多这样的研究中,医生们在拟行膝关节置换的患者中约50％使用了牛津单髁膝置换。     

Combining advanced radiotherapy technologies to maximize safety and tumor control probability in stage?III non-small cell lung cancer

BACKGROUND: The goal of the current study was to investigate the tumor control probability (TCP) of advanced radiotherapy technologies for stage?III non-small cell lung cancer (NSCLC) and to evaluate potential interplay effects between their applications. MATERIALS AND METHODS: Three-dimensional conformal radiotherapy (3D-CRT) with conventionally fractionated doses of 66?Gy served as reference for 13?patients with stage?III NSCLC. Isotoxic dose escalation relative to the corresponding 3D-CRT plans was performed for three technologies and their combinations: intensity-modulated radiotherapy (IMRT), IMRT with a simultaneous integrated boost (IMRT-SIB) of 10% to the gross tumor volume (GTV), and adaptive re-planning twice during the treatment course (ART). All analyses were based on accumulated dose distributions using deformable image registration of CT images, which were acquired weekly during the treatment course. RESULTS: IMRT reduced the mean lung dose (MLD) by 5.6%?±?3.8% compared to 3D-CRT. ART resulted in lung sparing of 7.9%?±?4.8% and 9.2%?±?3.9% in 3D-CRT and IMRT planning, respectively. IMRT and ART escalated the irradiation dose by 6.6%?±?3.2% and 8.8%?±?6.3%, respectively, which was not statistically different. For the 7?patients with the largest GTVs, IMRT-SIB was superior to IMRT and ART with dose escalation of 11.9%?±?3.7%. The combination of ART, IMRT, and SIB achieved maximum dose escalation in all 13?patients by 17.1%?±?5.4% on average, which increased TCP from 19.9%?±?7.0 to 37.1%?±?10.1%. Adaptive re-planning was required to continuously conform the escalated and hypofractionated SIB doses to the shrinking tumor. CONCLUSION: Combining advanced radiotherapy technologies is considered as a safe and effective strategy to maximize local tumor control probability in stage?III NSCLC.     

Does Exercise Improve Coronary Collateralization? A New Look at an Old Belief

In brief: An alternative route for blood supply in the heart—ie, coronary collateral vessels—can save the life of a person with coronary artery disease. Debate continues as to whether exercise training accelerates the growth of collateral vessels. Animal research has produced positive results, but studies of humans have been disappointing, largely because of problems in experimental design and methodology. Advances in technology—such as further refinements in radionuclide exercise testing methods—may help provide answers to this intriguing question.     

Return to work after heart transplantation: 12-year follow-up.

BACKGROUND: Current statistics show that 50% of heart transplantation recipients survive 10 years or more. Emphasis on cost containment has renewed interest in the employment status of these long-term survivors. METHODS: We have identified 62 patients operated on at one United Kingdom center and evaluated their employment and clinical status by interview at 1, 5, and 12 years from surgery. RESULTS: Employment pattern was good, with 69%, 69% (of 55 survivors), and 57% (of 35 survivors) of the group working at 1, 5, and 12 years, respectively. Blue-collar work status per se was not a deterrent to employment, but older patients with a poor presurgical work history were less successful in finding work, and trade and legislative restrictions forced some, who were willing and capable of returning to their previous employment, into lower paid, less satisfactory jobs. CONCLUSIONS: Subgroups of patients who are likely to be unemployed can be identified prior to surgery. Steps can be taken prior to surgery to anticipate future problems, and establish realistic employment goals.     

Antihypertensive drugs, dietary salt, and renal protection: how low should you go and with which therapy?

Although it is clear that hypertension accelerates the rate of progression of most forms of chronic renal disease, many unanswered questions remain concerning how to optimally preserve kidney function in patients with hypertension and renal insufficiency. The mechanisms by which hypertension accelerates progression of renal disease have been extensively studied in experimental models. Glomerular capillary hypertension, consequent to an increase in systemic blood pressure combined with a reduction in preglomerular resistance and/or an increase in postglomerular resistance, results in increased hydraulic stress to the glomerular capillary wall. This and other mechanisms result in the release of growth-promoting cytokines and soluble mediators of fibrosis that stimulate cellular proliferation and matrix accumulation, ultimately leading to glomerular sclerosis and interstitial fibrosis. Almost without exception, studies in animals demonstrate that blood pressure reduction reduces the rate of progression of experimental renal disease. Angiotensin-converting enzyme inhibitors and, possibly, calcium antagonists may have a therapeutic advantage compared with other antihypertensive drugs in preventing kidney damage. This has been linked to both blood pressure-dependent and -independent actions. However, most experimental studies have failed to reduce blood pressure to a level sufficient to establish the clinical relevance of potential blood pressure-independent effects. Experimental studies comparing various types of antihypertensive drugs in which a mean arterial pressure (MAP) of approximately 92 mm Hg is achieved are necessary to determine whether clinically important differences in the effects of these drugs on the rate of progression of renal disease exist. Clinical experience with high blood pressure and kidney disease in humans suggests that the risk of developing hypertension-associated renal disease is a continuous variable across the entire range of systolic and diastolic blood pressures. Logically, optimal protection of kidney function may therefore be a continuous function of declining systemic blood pressure. Consistent with this view, recent clinical trials suggest that reducing MAP to 92 mm Hg, corresponding to a blood pressure reading of 125/75 mm Hg, provides more optimal stabilization of renal function in patients with nondiabetic proteinuric kidney disease (>1 g/d) compared with more conventional therapy with a blood pressure goal of 140/90 mm Hg (MAP 107 mm Hg). Clinical trials in patients with diabetes mellitus and renal insufficiency also demonstrate the benefits of reducing blood pressure to approximately 95 mm Hg MAP. Dietary salt consumption may be another important variable affecting the rate of progression of renal disease due to both direct, salt-dependent effects on renal growth and the action of decreased salt intake to augment the antihypertensive and antiproteinuric properties of many drugs. The precise role of alterations in dietary salt consumption on progression of renal disease directly as well as on the effectiveness of various antihypertensive drugs has yet to be examined in clinical trials.     

Effect of the number of projections collected on quantitative perfusion and left ventricular ejection fraction measurements from gated myocardial perfusion single-photon emission computed tomographic images

Background

Gated myocardial perfusion single-photon emission computed tomographic (SPECT) imaging is currently performed by step-and-shoot detector rotation, resulting in acquisition dead time and lengthened study duration compared with nongated SPECT imaging with continuous or pseudocontinuous rotation. Dead time is particularly undesirable in new fast-gated SPECT imaging protocols with inotropic pharmacologic stress.

Methods and Results

This article evaluated the influence of projections’ angular spacing on quantitative measurements of left ventricular ejection fraction (LVEF) and perfusion from postexercise ^99mTc-labeled sestamibi images. Gated 60-projection data sets from 30 patients were compacted into 30- and 15-projection sets. The three sets (corresponding to 3-, 6-, and 12-degree spacing over 180 degrees) were reconstructed into gated and ungated short-axis image sets. LVEFs were measured from the gated images according to a previously described automatic algorithm, whereas perfusion was assessed from the ungated images by a 20-segment division of their maximal pixel polar maps. LVEF values were essentially unchanged between 60- and 30-projection images (y=0.37+0.996x; r=0.999; standard error of the estimate=0.56) and 60- and 15-projection images (y=1.35+0.987x; r=0.999; standard error of the estimate=0.77) in the 30 patients. Overall, 30- and 15-projection polar maps differed by 1.87%±1.24% and 4.38%±2.25% from the 60-projection polar maps, respectively. Segmental perfusion score agreement between 60- and 30-projection images and between 60- and 15-projection images was 93% (κ=0.92; p<0.001) and 83% (κ=0.81; p<0.001), respectively. Sixty- and 30-projection images were visually undistinguishable, whereas loss of image resolution was noticed in many 15-projection gated and ungated images.

Conclusions

Thirty-projection gated SPECT imaging is a practical, accurate, and time-saving approach in standard gated protocols and, potentially, fast-gated protocols. Fifteen-projection gated SPECT imaging is not generally recommended and should be considered only for LVEF assessment in conjunction with fast-gated protocols.     

The effects of antihistamines with varying anticholinergic properties on voluntary and involuntary movement

ObjectiveRecent evidence indicates that antihistamines can affect movement, which is most likely due to altered neurotransmission in cholinergic and histaminergic pathways. The purpose of this study was to determine if antihistamines with varying anticholinergic properties differentially affect voluntary and involuntary movement control.MethodsEleven healthy subjects were enlisted into a human double blind, placebo-controlled, five-way crossover study. Drowsiness, reaction time, and physiological tremor were examined 1-, 2-, and 3-hr post-ingestion of antihistamines with known anticholinergic profiles. These were the first-generation promethazine, and second-generation loratadine, desloratadine, and fexofenadine. Hyoscine butylbromide was used in an additional experiment to determine how a peripheral antimuscarinic drug influenced neuromotor function.ResultsPromethazine, desloratadine and fexofenadine increased drowsiness. Promethazine increased simple and choice reaction time and reduced tremor. Desloratadine increased choice reaction time and tremor, while loratadine slowed simple and choice reaction time.ConclusionCentral anticholinergic and antihistaminergic properties of antihistamines potentially contribute to movement dysfunction.SignificanceSecond-generation antihistamines have provided the consumer with a safer alternative to the first-generation sedating antihistamine. However, the results of this study suggest that loratadine and desloratadine have the potential to affect movement control, and further research is warranted to understand the clinical relevance of these findings.     

High titer anti-HIV antibody reactivity associated with a paraprotein spike in a homosexual male with AIDS related complex

We observed a human immunodeficiency virus (HIV)-infected homosexual male with AIDS related complex (ARC) who had a serum globulin level of 80 g/L. Serum protein electrophoresis revealed a gamma globulin fraction of 40 g/L, of which 50% (20 g/L) was contained within a paraprotein spike, comprised predominantly of IgG kappa. This patient also had high titer anti-HIV antibodies in his serum, which were Western blot reactive at a final dilution of 1:500,000, and recognized gp120env, p66pol, p55gag, p53pol, p41gag, and p24gag. Because paraproteins in the past have been shown to be directed against specific antigens, we purified this patient's paraprotein using a modified high performance liquid chromatography (HPLC)-hydroxylapatite procedure and tested the purified paraprotein for anti-HIV antibody activity. The purified paraprotein retained anti-HIV antibody activity to a final dilution of 1:100,000, and recognized p66pol, p55gag, p53pol, p41gag, and p24gag. The recognition of both "gag" and "pol" gene products suggested that the purified paraprotein might not be monoclonal in origin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that the purified paraprotein contained at least two immunoglobulin light chain species (Mol wt 30 to 33 Kd). Affinity chromatography of the purified paraprotein using a p24- Sepharose 4B matrix separated the "gag" and "pol" antibody activities. Immunoglobulin gene rearrangement analysis of a bone marrow aspirate (which contained 15% plasma cells) failed to reveal a clonal population of immunoglobulin producing cells. We conclude that this patient's paraprotein accounted for most of the anti-HIV activity present in whole serum, and that this paraprotein was not monoclonal in origin.     

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband–parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P=1.5 × 10⁻⁴). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P=0.018) and de novo mutations (P=0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N=614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.