Gait analysis of walking before and after medial opening wedge high tibial osteotomy

Introduction

Medial opening wedge high tibial osteotomy (HTO) is used to treat medial compartment osteoarthritis (OA) of the knee. HTO shifts the weight-bearing line from the medial compartment into the lateral compartment. The aim of this study was to investigate the functional biomechanical consequences of this alteration in alignment.

Methods

Eleven male patients with medial compartment osteoarthritis underwent three-dimensional gait analysis during level walking before 12 months and after medial opening wedge HTO. Nine male control subjects of a similar age were also tested using the same protocol. Sagittal and coronal angles and moments in both operated and non-operated knees were compared. Pre and postoperative radiographic coronal plane alignment was also measured.

Results

Walking speed increased significantly postoperatively (P = 0.0001) and was not different from controls. Preoperatively, maximum knee flexion in stance was reduced compared to control (P = 0.02). Postoperatively, maximum knee flexion increased significantly (P = 0.005) and was the same as the controls. Similar changes were observed for the maximum knee flexion moment. The mean maximum varus angle during stance was reduced from 13.5° preoperatively to 5.4° postoperatively (P = 0.0001) compared to (6.8°) in controls. The mean maximum adduction moment also reduced from 3.9 to 2.7 (% Bw/ht, P = 0.02), compared to 3.6 in control subjects. Interestingly, the adduction moments in the non-operated knee increased postoperatively from 3.3 to 4.1 (% Bw/ht, P = 0.02). The mean radiological mechanical alignment was changed from 172 degrees preoperatively to 180 degrees postoperatively (P < 0.001).

Conclusion

HTO resulted in normalisation of several dynamic knee function parameters such as walking speed, knee flexion and external knee flexion moment. As anticipated, HTO reduced the varus angle and adduction moments of the operated knee. An increased adduction moment in the non-operated knee over the first postoperative year was found.

Level of evidence

Prospective case–control clinical laboratory study, Level III.     

Nitric oxide interactions with cobalamins: biochemical and functional consequences

Nitric oxide (NO) is a paramagnetic gas that has been implicated in a wide range of biologic functions. The common pathway to evoke the functional response frequently involves the formation of an iron- nitrosyl complex in a target (heme) protein. In this study, we report on the interactions between NO and cobalt-containing vitamin B12 derivatives. Absorption spectroscopy showed that of the four Co(III) derivatives (cyanocobalamin [CN-Cbl], aquocobalamin [H2O-Cbl], adenosylcobalamin [Ado-Cbl], and methylcobalamin [MeCbl]), only the H2O- Cbl combined with NO. In addition, electron paramagnetic resonance spectroscopy of H2O-Cbl preparations showed the presence of a small amount of Cob-(II)alamin that was capable of combining with NO. The Co(III)-NO complex was very stable, but could transfer its NO moiety to hemoglobin (Hb). The transfer was accompanied by a reduction of the Co(III) to Co(II), indicating that NO+ (nitrosonium) was the leaving group. In accordance with this, the NO did not combine with the Hb Fe(II)-heme, but most likely with the Hb cysteine-thiolate. Similarly, the Co(III)-NO complex was capable of transferring its NO to glutathione. Ado-Cbl and Me-Cbl were susceptible to photolysis, but CN- Cbl and H2O-Cbl were not. The homolytic cleavage of the Co(III)-Ado or Co(III)-Me bond resulted in the reduction of the metal. When photolysis was performed in the presence of NO, formation of NO-Co(II) was observed. Co(II)-nitrosyl oxidized slowly to form Co(III)-nitrosyl. The capability of aquocobalamin to combine with NO had functional consequences. We found that nitrosylcobalamin had diminished ability to serve as a cofactor for the enzyme methionine synthase, and that aquocobalamin could quench NO-mediated inhibition of cell proliferation. Our in vitro studies therefore suggest that interactions between NO and cobalamins may have important consequences in vivo.     

Autobiographical memory in mild cognitive impairment and Alzheimer's disease: A comparison between the Levine and Kopelman interview methodologies

Previous studies have produced inconsistent results concerning the two components of autobiographical memory—personal semantic memory and episodic memory. Results in subjects with mild cognitive impairment (MCI) and dementia of Alzheimer's type (DAT) have varied concerning the existence of a temporal gradient in retrograde amnesia. These results have important theoretical implications regarding multiple trace theory versus standard consolidation models of long‐term memory (LTM). We investigated whether this variability arises from differences in the methods used in assessing autobiographical memory. We examined patterns of memory impairment in 20 healthy elderly controls, 20 MCI subjects, and 10 DAT subjects using the Autobiographical Memory Interview (AMI) of Kopelman and the Autobiographical Interview (AI) of Levine. Both the AMI and AI were modified to allow for the test scores to be derived from a single interview without fatiguing the subjects. On the AMI, DAT subjects were significantly impaired on both components of autobiographical memory—episodic memory and personal semantics—with episodic memory showing a significant though gentle temporal gradient sparing childhood memories. Using the AI test, subjects with DAT showed impaired recall of episodic details (but not personal semantics), again with a gentle temporal gradient. Differences between the two interview methods (fewer epochs in the AMI; fewer memories per epoch in the AI) were found to have a significant impact on the pattern of findings; fewer epochs in the AMI brought out the temporal gradient, and fewer memories per epoch (in the AI) diminished it. These data show the importance of technical details of the different tests in favouring one versus another LTM theory. The data are not purely compatible with either theory. © 2012 Wiley Periodicals, Inc.     

Effect of long-term estrogen therapy on dopaminergic responsivity in post-menopausal women--a preliminary study

Females have a higher prevalence than men of neuropsychiatric disorders in which dopaminergic abnormalities play a prominent role, e.g. very late-onset schizophrenia and Parkinson’s disease (PD). The biological basis of these sex differences is unknown but may include modulation of the dopaminergic system by sex hormones, as there is preliminary evidence that estrogen modulates treatment response in these disorders. Furthermore, sex differences in dopamine-mediated cognitive decline suggest estrogen may also play a role in healthy aging. However, the effects of estrogen on the dopaminergic system are poorly understood, and nobody has examined the effect of long-term estrogen therapy (ET) on this system. We compared dopaminergic responsivity (growth hormone (GH) response to apomorphine) in post-menopausal women on ET to women who were ET-naïve. GH response to subcutaneous apomorphine (0.005 mg/kg) was measured in two groups of healthy post-menopausal women aged between 55 and 70 years: those taking ET (n=13) and those who had never taken ET (n=13). Neither group was taking any other medication. GH was measured at 15 min intervals from −30 min before administration of apomorphine to 90 min post-administration. GH response was measured in two ways: area under the curve (AUC) and maximum response over baseline (GH). There were no between-group differences in demographic or baseline variables. The ET treated women had a significantly greater (p=0.03) AUC than ET naïve women (mean±S.D.; 5.3±4.7 vs. 2.6±2.3). However, (GH) did not differ significantly between groups (6.1 mU/l±6.2 vs. 2.7 mU/l±S.D.=4.1). Also, analysis of GH response over time revealed a significant main effect of time (p<0.0005), and a group by time interaction (p=0.004), but no significant main effect of group. Our results suggest that ET may enhance dopaminergic responsivity in post-menopausal women. Estrogen deficiency following menopause may partly explain age and gender differences in late-onset neuropsychiatric disorders.     

One‐ and two‐stage design proposals for a phase II trial comparing three active treatments with control using an ordered categorical endpoint

Phase II clinical trials are performed to investigate whether a novel treatment shows sufficient promise of efficacy to justify its evaluation in a subsequent definitive phase III trial, and they are often also used to select the dose to take forward. In this paper we discuss different design proposals for a phase II trial in which three active treatment doses and a placebo control are to be compared in terms of a single‐ordered categorical endpoint. The sample size requirements for one‐stage and two‐stage designs are derived, based on an approach similar to that of Dunnett. Detailed computations are prepared for an illustrative example concerning a study in stroke. Allowance for early stopping for futility is made. Simulations are used to verify that the specified type I error and power requirements are valid, despite certain approximations used in the derivation of sample size. The advantages and disadvantages of the different designs are discussed, and the scope for extending the approach to different forms of endpoint is considered. Copyright © 2008 John Wiley & Sons, Ltd.     

Can an 18-point clock-drawing scoring system predict dementia in elderly individuals with mild cognitive impairment?

The purpose of this study was to develop a clock-drawing scoring system better suited to detecting possible early markers of dementia in individuals with mild cognitive impairment (MCI). We modified the scoring system of Freedman et al. (1994), in which the major components are integrity of the circle, placement and size of the hands, and placement and sequence of the numbers. We rescored the clock-drawing test using a novel 18-point scoring system, which emphasizes hand elements-number of hands, direction indicated, and size differences. We retrospectively assessed 123 individuals (ages 58-88 years) selected from the Memory Clinic at the Jewish General Hospital in Montreal. These consisted of 21 normal elderly individuals (NORM group), 41 participants with mild cognitive impairment who did not develop dementia on follow-up visits (MCI-NP), 41 participants with mild cognitive impairment who became demented after a 48-month follow-up (MCI-D), and 20 participants diagnosed with Alzheimer's disease (AD). On the 18-point system, the MCI-NP and the MCI-D did not show any difference on overall total score (p = .166), However, using Pearson chi-squares to examine the within-categories effects comparing the mildly cognitively impaired groups (MCI-NP and MCI-D), there were three significant hand items that appear to be possible early markers of progression to dementia. The clock has two hands (p = .043), hour hand is towards correct number (p = .023), and size difference of the hands is respected (p = .004), all showed significant differences between progressors and nonprogressors. The 18-point clock-drawing scoring system may have advantages in better indicating MCI individuals more likely to progress to dementia.     

Aripiprazole versus haloperidol treatment in early-stage schizophrenia

We conducted a secondary analysis of a completed study of the differential efficacy and side effects of aripiprazole versus haloperidol in early-stage schizophrenia (ESS), a subpopulation of patients which does not include first episode or chronic patients. A subpopulation of 360 individuals with ESS were identified from a randomized, multi-center, double-blind study of 1294 individuals with schizophrenia at different stages of illness who were randomized to treatment with aripiprazole (ESS = 237) or haloperidol (ESS = 123) for one year. The primary outcome measure was response rate based on a 50% reduction of Positive and Negative Syndrome Scale (PANSS) total scores. Secondary outcomes included several efficacy and safety measures, as well as treatment discontinuation. More individuals in the aripiprazole group (48%) than in the haloperidol group (28%; p < 0.01) completed the study. Response rates were greater in the aripiprazole group (38% [N = 91]) than in the haloperidol group (22% [N = 27]; p < 0.01). Aripiprazole was associated with fewer extrapyramidal side effects. ESS subjects in the haloperidol group were more likely than those in the aripiprazole group to discontinue the study drug due to an adverse event other than worsening illness (29% and 11%, respectively; p < 0.01), and efficacy differences were reduced by interventions to mitigate side effects (decreasing antipsychotic dose with or without adding antiparkinsonian medication). Aripiprazole has a favorable efficacy/safety profile in ESS and appeared to be superior to haloperidol on a number of efficacy and safety outcomes. However, excessive dosing of the antipsychotic medications, in particular haloperidol, may have played an important role in accounting for the differences between aripiprazole and haloperidol in this study.