Assessment of contrast‐enhanced computed tomography for imaging of cartilage during fracture healing

Assessment of the early stages of fracture healing via X‐rays and computed tomography is limited by the low radio‐opacity of cartilage. We validated a method of contrast‐enhanced computed tomography (CECT) for non‐destructive identification of cartilage within a healing fracture callus. Closed, stabilized fractures in femora of C57BL/6 mice were harvested on post‐operative day 9.5 and imaged ex vivo with micro‐computed tomography (µCT) before and after incubation in a cationic contrast agent that preferentially accumulates in cartilage due to the high concentration of sulfated glycosaminoglycans in the tissue. Co‐registration of the pre‐ and post‐incubation images, followed by image subtraction, enabled two‐ and three‐dimensional delineation of mineralized tissue, soft callus, and cartilage. The areas of cartilage and callus identified with CECT were compared to those identified with the gold‐standard method of histomorphometry. No difference was found between the areas of cartilage measured by the two methods (p = 0.999). Callus area measured by CECT was smaller than, but strongly predictive of (R² = 0.80, p < 0.001), the corresponding histomorphometric measurements. CECT also enabled qualitative identification of mineralized cartilage. These findings indicate that the CECT method provides accurate, quantitative, and non‐destructive visualization of the shape and composition of the fracture callus, even during the early stages of repair when little mineralized tissue is present. The non‐destructive nature of this method would allow subsequent analyses, such as mechanical testing, to be performed on the callus, thus enabling higher‐throughput, comprehensive investigations of bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 567–573, 2013     

From inhibition to activation,from emotional hyporeactivity to emotional hyperreactivity: Two pathways to discriminate mood in bipolar disorders

To better explore the clinical heterogeneity of bipolar mood states, we developed a dimensional scale for assessing all mood episodes (depressive, hypomanic, manic, mixed states) using the same tool. The Multidimensional Assessment of Thymic States (MATHYS) (Henry et al., 2008) provides two scores, a total score measuring a level of activation and a sub-score of emotional reactivity. The aim of this study was to establish the appropriate cut-off in total activation versus inhibition and in the emotional reactivity sub-score in bipolar disorders. Patients (n=187) during an acute episode and controls (n=89) filled in the MATHYS. Receiver Operating Characteristic (ROC) curves were obtained to estimate the sensitivity and specificity of the global score and the emotional reactivity sub-score of the MATHYS, in order to differentiate patients from controls. ROC curves showed very satisfactory sensitivity and specificity levels both for the total score and the sub-score of emotional reactivity, thus providing an appropriate cut-off. Concerning the total score between 0 and 200, patients with a score lower than 91 had significant global inhibition and those with a score higher than 109 had significant global activation. Regarding the emotional reactivity sub-score between 0 and 40, patients with a score lower than 16 had significant emotional hyporeactivity and those with a score higher than 24 had significant emotional hyperreactivity. Our results provide cut-offs for the MATHYS to identify patients in an acute phase.     

Transfer of training effects in stroke patients with apraxia: An exploratory study

The goal of the present study was to examine the transfer of the effects of cognitive strategy training for stroke patients with apraxia from trained to non-trained tasks. In strategy training, the occurrence of transfer is expected as the training programme is aimed, not at relearning specific tasks, but at teaching patients new ways to handle the problems resulting from the impairment. Exploratory analyses were conducted on data previously collected in a randomised controlled trial on the efficacy of the strategy training. A total of 113 left hemisphere stroke patients were randomly assigned to a strategy training group and a group receiving occupational therapy as usual. Assessment of apraxia, motor functioning and activities of daily living (ADL) took place at baseline, after an eight-week treatment period, and five months after baseline. The primary outcome measure consisted of standardised ADL observations of trained and non-trained tasks. The analyses showed that in both treatment groups, the scores on the ADL observations for non-trained tasks improved significantly after eight weeks of training as compared with the baseline score. Change scores of non-trained activities were larger in the strategy training group as compared with the usual treatment group.

By using previously collected data we are able to illustrate the potential transfer of treatment effects in a large sample of stroke patients. We found indications for the occurrence of transfer, although the study was not originally designed for the purpose of evaluating transfer. Therefore these results are worth exploring more profoundly. We will further investigate our preliminary conclusions in a new prospective study which is specifically designed to examine the transfer of training effects.     

A case study evaluation of the effects of different techniques for the treatment of anomia

Abstract

This study sought to demonstrate the relative effects of different techniques for treatment of the severe anomia of a 67 year-old aphasic woman. Both a semantic and a word form problem underlaid the anomia. A single subject approach was employed with an alternating treatment design to contrast four therapy conditions and two control conditions. Condition 1 involved semantic matching tasks and word form training (mentally visualising the written word, naming with the help of the first letter), condition 2 involved semantically unrelated matching tasks and word form training, condition 3 involved semantic matching tasks, condition 4 involved semantically unrelated matching tasks. In the two control conditions, the patient was only provided with the opportunity to try to name the pictures. With the first therapy condition, the criterion for the termination of therapy was reached. Moreover, there were overall significant differences between the different conditions. Some maintenance of the effects of therapy were observed two days later. No generalisation to untreated items was observed, although the patient seemed to be better at identifying the first syllables of words when naming. These results demonstrate that techniques which are designed for remediating particular anomic problems are a better means of therapy than techniques which are not.     

Contributions of the hippocampal subfields and entorhinal cortex to disambiguation during working memory

The hippocampus and medial temporal lobes (MTL) support the successful formation of new memories without succumbing to interference from related, older memories. Computational models and animal findings have implicated the dentate gyrus (DG), CA3, CA1, and entorhinal cortex (EC) in the disambiguation and encoding of well‐established, episodic events that share common elements. However, it is unknown if these hippocampal subfields and MTL (entorhinal, perirhinal, parahippocampal) cortices also contribute during working memory when overlapping stimuli that share related features are rapidly encoded and subsequently maintained over a brief temporal delay. We hypothesized that activity in CA3/DG hippocampal subfields would be greater for the rapid encoding of stimuli with overlapping features than for the rapid encoding of stimuli with distinct features. In addition, we predicted that CA1 and EC, regions that are associated with creating long‐term episodic representations, would show greater sustained activity across both encoding and delay periods for representations of stimuli with overlapping features than for those with distinct features. We used high‐resolution fMRI during a delayed matching‐to‐sample (DMS) task using face pairs that either shared (overlapping condition, OL) or did not share (non‐overlapping condition, NOL) common elements. We contrasted the OL condition with the NOL condition separately at sample (encoding) and during a brief delay (maintenance). At sample, we observed activity localized to CA3/DG, the subiculum, and CA1. At delay, we observed activity localized to the subiculum and CA1 and activity within the entorhinal, perirhinal, and parahippocampal cortices. Our findings are consistent with our hypotheses and suggest that CA3/DG, CA1 and the subiculum support the disambiguation and encoding of overlapping representations while CA1, subiculum and entorhinal cortex maintain these overlapping representations during working memory. © 2013 Wiley Periodicals, Inc.     

Ontogeny of the Therapeutic Alliance in Borderline Patients

The development of the therapeutic alliance is explored in a prospective study of 33 borderline personality disorder patients. Assessments of the alliance were made by both the patients and their therapists using the Penn Helping Alliance Questionnaire at six weeks, six months, and then annually for up to five years.The major findings were: (1) The alliance was rated highly by both patients and therapists throughout treatment; (2) the alliance showed steady and significant improvement over time (and no significant deterioration at any point); (3) patients and therapists corresponded closely in their assessments; (4) therapists rated the alliance higher than did patients at three and four years; (5) therapist ratings of the alliance at six weeks was predictive of subsequent dropping out; but (6) early alliance scores were not strongly related to subsequent level of change. These results frame issues for future research in this area.Die Entwicklung der therapeutischen Allianz wurde in einer prospektiven Studie bei 33 Patienten mit Borderline-Persönlichkeitsstörungen überprüft. Die Einschätzungen der Allianz wurden sowohl von den Patienten als auch von ihren Therapeuten mit Hilfe des Penn Helping Alliance Fragbogens nach sechs Wochen, sechs Monaten und dann jährlich über den Zeitraum von fünf Jahren vorgenommen.Die Ergebnisse der Studie sind: 1) Die Allianz wurde sowohl von den Patienten als auch von den Therapeuten über die gesamte Behandlung hinweg hoch eingeschätzt; 2) Die Allianz verbesserte sich stetig und signifikant innerhalb des Behandlung-szeitrwams und wies keine signifkante Verschlechterung an irgendeiner Stelle des Prozesses auf; 3) Patienten und Therapeuten stimmten in ihren Einschätzungen weitgehend überein; 4) Therapeuten schätzten die Allianz im dritten und vierten Jahr höher ein als die Patienten; 5) Die Einschätzung der therapeutischen Allianz nach sechs Wochen durch den Therapeuten kann spétere Therapieabbrüche vorhersagen, aber 6) die frühen Allianzwerte waren nicht sehr ausgeprägt bezogen auf spätere Veränderungswerte. Die Ergebnisse stecken den Rahmen für zukünftige Studien in diesem Bereich ab.Le développement de l'alliance thérapeutique est exploré dans une étude prospective sur 33 patients avec trouble de la personnalité borderline. Des évaluations de l'alliance ont été faites par les patients et leur thérapeute à l'aide du Questionnaire Penn Helping Alliance, à six semaines, six mois et ensuite annuellement pendant cinq ans.Les découvertes majeures ont été: 1) L'alliance a été à évaluée ‘forte’ à la fois par les patients et les thérapeutes pendant le traitement; 2) L'alliance a montré une amélioration stable et significative à travers le temps (et à aucun moment il n'y a eu de détérioration significative); 3) Les évaluations des patients et des thérapeutes correspondaient fortement; 4) Les thérapeutes ont évalués l'alliance plus forte que l'ont fait les patients aprés trois et quat ans; 5) Les évaluations de l'alliance par les thérapeutes étaient prédictives d'un subséquent désistement; mais 6) Les scores de l'alliance précoce n'étaient pas fortement liés à un subséquent niveau de changement. Ces résultats formulent des points intéressants de discussion pour de futures recherches dans ce domaine.     

Adrenoleukodystrophy in Norway: High Rate of De Novo Mutations and Age-Dependent Penetrance

To investigate X-linked adrenoleukodystrophy in an unselected population, we performed a population based, cross-sectional prevalence study, supplemented by a retrospective study of deceased subjects. Sixty-three subjects (34 males, 29 females) belonging to 22 kindreds were included. Thirty-nine subjects (13 males, 26 females) were alive, and 24 (21 males, 3 females) were deceased on the prevalence day. The point prevalence of X-linked adrenoleukodystrophy in Norway on July 1, 2011, was 0.8 per 100,000 inhabitants. The incidence at birth in the period 1956-1995 was 1.6 per 100,000 inhabitants. An age-dependent penetrance was observed among males and females, with more severe phenotypes appearing with rising age. Only 5% of deceased males had not developed cerebral leukodystrophy. No female older than 50 years was neurologically intact. Sixteen mutations in the ABCD1 gene were identified. De novo mutations were found in 19% of probands. The frequency of X-linked adrenoleukodystrophy was lower in Norway than reported in the literature. A more severe natural course than previously reported was observed, indicating a need for better follow-up of both male and female patients. Given the high rate of de novo mutations, identification programs such as newborn screening may be required to offer timely treatment to all patients.     

Markers of insulin resistance in Polycystic ovary syndrome women: An update

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting 5%-10% of women of reproductive age. The importance of this syndrome lies in the magnitude of associated comorbidities: infertility, metabolic dysfunction, cardiovascular disease (CVD), plus psychological and oncological complications. Insulin resistance (IR) is a prominent feature of PCOS with a prevalence of 35%-80%. Without adequate management, IR with compensatory hyperinsulinemia contributes directly to reproductive dysfunction in women with PCOS. Furthermore, epidemiological data shows compelling evidence that PCOS is associated with an increased risk of impaired glucose tolerance, gestational diabetes mellitus and type 2 diabetes. In addition, metabolic dysfunction leads to a risk for CVD that increases with aging in women with PCOS. Indeed, the severity of IR in women with PCOS is associated with the amount of abdominal obesity, even in lean women with PCOS. Given these drastic implications, it is important to diagnose and treat insulin resistance as early as possible. Many markers have been proposed. However, quantitative assessment of IR in clinical practice remains a major challenge. The gold standard method for assessing insulin sensitivity is the hyperinsulinemic euglycemic glucose clamp. However, it is not used routinely because of the complexity of its procedure. Consequently, there has been an urgent need for surrogate markers of IR that are more applicable in large population-based epidemiological investigations. Despite this, many of them are either difficult to apply in routine clinical practice or useless for women with PCOS. Considering this difficulty, there is still a need for an accurate marker for easy, early detection and assessment of IR in women with PCOS. This review highlights markers of IR already used in women with PCOS, including new markers recently reported in literature, and it establishes a new classification for these markers.