Jens Dreyhaupt

Mineral Trioxide Aggregate or Calcium Hydroxide Direct Pulp Capping: An Analysis of the Clinical Treatment Outcome

INTRODUCTION The use of mineral trioxide aggregate (MTA) might improve the prognosis of teeth after pulp exposure. The treatment outcome of teeth after direct pulp capping, either with mineral trioxide aggregate (MTA) or calcium hydroxide (controls), was investigated, taking into account possible confounding factors. METHODS One hundred forty-nine patients treated between 2001 and 2006 who received direct pulp capping treatment in 167 teeth met the inclusion criteria. Treatment was performed by supervised undergraduate students (72%) and dentists (28%). Assessment of clinical and radiographic outcomes was performed by calibrated examiners 12-80 months after treatment (median, 27 months). RESULTS One hundred eight patients (122 treated teeth) were available for follow-up (72.5% recall rate). A successful outcome was recorded for 78% of teeth (54 of 69) in the MTA group and for 60% of teeth (32 of 53) in the the calcium hydroxide group. The univariate analysis (generalized estimation equations model [GEE model] showed a significant difference in the success rate (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.05-5.32; P = .04). In the multiple analysis (GEE model), the OR is marginally inside the nonsignificant range (OR, 0.43; 95% CI, 0.19-1.02; P = .05) when conspicuous confounding factors are stabilized (univariate analysis). Multiple analysis showed that teeth that were permanently restored >or=2 days after capping had a significantly worse prognosis in both groups (OR, 0.24; 95% CI, 0.09-0.66; P = .01). CONCLUSIONS MTA appears to be more effective than calcium hydroxide for maintaining long-term pulp vitality after direct pulp capping. The immediate and definitive restoration of teeth after direct pulp capping should always be aimed for.

Dry Powder Inhalers: Which Factors Determine the Frequency of Handling Errors?

Background: Dry powder inhalers are often used ineffectively, resulting in a poor level of disease control. Objectives: To determine how often essential mistakes are made in the use of Aerolizer®, Discus®, HandiHaler® and Turbuhaler® and to study the effects of age, severity of airflow obstruction and previous training in inhalational technique by medical personnel on the error rate. Methods: Two hundred and twenty-four newly referred outpatients (age 55.1 ± 20 years) were asked how they had been acquainted with the inhaler and to demonstrate their inhalational technique. Results: The inhaler-specific error rates were as follows: Aerolizer 9.1%, Discus 26.7%, HandiHaler 53.1% and Turbuhaler 34.9%. Compared to Aerolizer, the odds ratio of an ineffective inhalation was higher for HandiHaler (9.82, p < 0.01) and Turbuhaler (4.84, p < 0.05). The error rate increased with age and with the severity of airway obstruction (p < 0.01). When training had been given as opposed to no training, the odds ratio of ineffective inhalation was 0.22 (p < 0.01). If Turbuhaler is used, the estimated risks range from 9.8% in an 18-year-old patient with normal lung function and previous training to 83.2% in an 80-year-old patient with moderate or severe obstruction who had not received any training. Conclusions: Dry powder inhalers are useful in the management of younger patients with normal lung function or mild airway obstruction. In older patients with advanced chronic obstructive pulmonary disease, the risk of ineffective inhalation remains high despite training in inhalational technique. A metered-dose inhaler with a spacer might be a valuable treatment alternative in a substantial proportion of these patients.

Anatomic Reconstruction of the Medial Patellofemoral Ligament in Children and Adolescents With Open Growth Plates Surgical Technique and Clinical Outcome

Background: Recurrent lateral patellar dislocation is a common knee injury in the skeletally immature adolescent. Because of the open physis, operative therapy in children is challenging. This study presents the outcomes of a minimally invasive technique for anatomic reconstruction of the medial patellofemoral ligament (MPFL) in children that respects the distal femoral physis. Hypothesis: Anatomic reconstruction of the MPFL in children that maintains the distal femoral physis will prevent redislocation, preserve the distal femoral physis, and improve knee function. Study Design: Case series; Level of evidence, 4. Methods: Twenty-one consecutive patients with patellofemoral instability and open growth plates underwent anatomic reconstruction of the MPFL that maintained the distal femoral growth plate. Preoperative radiographic examination included AP and lateral views to assess patella alta and limb alignment. Magnetic resonance imaging was performed to evaluate trochlear dysplasia and tibial tubercle–trochlear groove (TT-TG) distance. Evaluation included preoperative and postoperative physical examination, Kujala score, and Tegner activity score. Results: The average age at the time of operation was 12.2 years (range, 10.3-13.9). The average follow-up after operation was 2.8 years after surgery (range, 2.0-3.6). No recurrent dislocation occurred, but 2 patients with high-grade trochlear dysplasia still had a positive apprehension sign. The Kujala score significantly improved from 72.9 (range, 37-87) preoperatively to 92.8 (range, 74-100) postoperatively (P < .01). The Tegner activity score decreased, but not significantly, from 6.0 (range, 3-9) preoperatively to 5.8 (range, 3-9) postoperatively (P = .48). Conclusion: Anatomic reconstruction of the MPFL that respects the distal femoral physis in skeletally immature patients is a safe and effective technique for the treatment of patellofemoral instability and allows patients to return to sports without redislocation of the patella.

Observer Agreement on the Dejour Trochlear Dysplasia Classification A Comparison of True Lateral Radiographs and Axial Magnetic Resonance Images

Background: Trochlear dysplasia is known to be an important cause of patellofemoral instability. D. Dejour’s radiographic and magnetic resonance imaging (MRI) classifications are widely used in clinical practice and in the orthopaedic literature to assess the severity of trochlear dysplasia. The indication for deepening trochleoplasty to treat trochlear dysplasia is also mainly based on the severity of trochlear dysplasia according to Dejour’s criteria. Purpose: To our knowledge, there is no study evaluating the efficacy of the Dejour classification. The aim of this study was to assess the intraobserver and interobserver agreements of the radiographic and MRI-based classification as described by Dejour. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: From 50 patients, 50 lateral radiographs as well as 50 MRI scans were read twice independently within 4 weeks by 4 surgeons (2 senior and 2 junior examiners). Analysis was made according to Dejour’s 4 grades of radiological criteria of trochlear dysplasia as well as differentiating between 2 grades: low-grade (type A) and high-grade trochlear dysplasia (types B-D). Results: The 4-grade analysis showed fair intraobserver and interobserver agreements (24%-78%), while the 2-grade analysis showed good to excellent agreement (56%-96%). The best overall agreement was found for the 2-grade analysis on MRI scans (62%-96%). The lateral radiographs tended to underestimate the severity of trochlear dysplasia compared with axial MRI. Conclusion: D. Dejour’s classification is valid for typing trochlear dysplasia and is particularly useful in separating low-grade from high-grade dysplasia.

A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis

Background Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). Methods/Principal Findings We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71–2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. Conclusion/Significance Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. Trial Registration Clinicaltrials.gov NCT00690118.

Treatment outcome of mineral trioxide aggregate: repair of root perforations.

INTRODUCTION The use of biocompatible materials like mineral trioxide aggregate (MTA) may improve the prognosis of teeth with root perforations. METHODS The treatment outcome of root perforations repaired between 2000 and 2006 with MTA was investigated. Twenty-six patients received treatment with MTA in 26 teeth with root perforations. Treatment was performed by supervised undergraduate students (29%), general dentists (52%), or dentists who had focused on endodontics (19%). Perforation repair by all treatment providers was performed using a dental operating microscope. Calibrated examiners assessed clinical and radiographic outcome 12 to 65 months after treatment (median 33 months, 81% recall rate). Pre-, intra-, and postoperative information relating to potential prognostic factors was evaluated. RESULTS Of 21 teeth examined, 18 teeth (86%) were classified as healed. None of the analyzed potential prognostic factors had a significant effect on the outcome. CONCLUSIONS MTA appears to provide a biocompatible and long-term effective seal for root perforations in all parts of the root.

Combined Trochleoplasty and Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocations in Severe Trochlear Dysplasia A Minimum 2-Year Follow-up Study

Background: Trochlear dysplasia is an important etiological factor for the development of patellofemoral instability. Because a dislocation of the patella as a result of trochlear dysplasia results in a traumatic disruption of the medial patellofemoral ligament (MPFL), a combined trochleoplasty and patellofemoral ligament reconstruction appears to be the most appropriate procedure to treat patients with severe trochlear dysplasia. Hypothesis: Combined trochleoplasty and anatomic reconstruction of the MPFL will prevent redislocations of the patella and will lead to improved knee function. Study Design: Case series; Level of evidence, 3. Methods: Twenty-three consecutive patients (26 knees) with patellofemoral instability and severe trochlear dysplasia underwent combined trochleoplasty and anatomic reconstruction of the MPFL. Preoperative radiographic examination included anteroposterior and lateral views to assess patella alta. Magnetic resonance imaging was performed to evaluate trochlear dysplasia and the tibial tubercle–trochlear groove (TT-TG) distance. Evaluations included the detection of cartilage injuries, preoperative and postoperative physical examinations, and scores for the visual analog scale (VAS), Kujala knee function, International Knee Documentation Committee (IKDC), activity rating scale (ARS), and Tegner activity scale. Results: The mean age at the time of operation was 19.2 years (range, 15.4-23.6 years). The mean follow-up after operation was 2.5 years after surgery (range, 2.0-3.5 years). No recurrent dislocation occurred postoperatively. Kujala scores improved from 79 to 96, IKDC scores from 74 to 90, and VAS scores from 3 to 1. All improvements were highly statistically significant (P < .01). The activity level according to the Tegner activity scale and the ARS decreased but was not statistically significant (P = .06 and P = .21, respectively). There were 95.7% of the patients who were satisfied or very satisfied with the procedure. Conclusion: Combined anatomic reconstruction of the MPFL and trochleoplasty reliably improved the stability of the patellofemoral joint in patients with severe trochlear dysplasia and no or mild degenerative changes. In addition, the described procedure showed significant improvement of knee function and good patient satisfaction without any episode of redislocations of the patella.

Reconstruction of the Medial Patellofemoral Ligament Clinical Outcomes and Return to Sports

Background: Recent studies have shown that medial patellofemoral ligament (MPFL) reconstruction using a standardized technique provides significant improvements in all outcome scoring systems, with low complication rates and good patient satisfaction. Although numerous studies have assessed clinical results, there is little published literature investigating return to sporting activities after reconstruction of the MPFL. Purpose: To demonstrate postoperative outcomes and the return-to-sports rate a minimum of 2 years after isolated MPFL reconstruction in a young patient cohort. Study Design: Case series; Level of evidence, 4. Methods: Between 2007 and 2010, a total of 72 isolated MPFL reconstructions (in 68 patients) were performed for recurrent patellar dislocation. Pre- and postoperative knee assessment included a thorough history of symptoms and a clinical examination consisting of crepitus, range of motion, patellofemoral pain, and patellar apprehension. Knee function was assessed using the Kujala score, International Knee Documentation Committee score, Tegner activity score, visual analog scale (VAS), and Activity Rating Scale (ARS). Results: Of patients who participated in sports preoperatively (62/68 patients), 100% returned to sports after MPFL reconstruction; 53% returned at equal or higher levels, whereas 47% returned at lower levels. Fifty-four of 68 patients (79.4%) rated themselves as very satisfied or satisfied with the results. The median Kujala score improved significantly from 66 to 87.5 and the median International Knee Documentation Committee score from 60 to 79.8. The median VAS for pain score illustrated significant preoperative to postoperative improvement, from 4 to 2. Conversely, patients’ activity levels according to the Tegner activity score dropped from 4.5 to 4, and the median Activity Rating Scale score dropped from 6 to 3. There was also a persistent instability rate of 10% as well as a slight loss of knee flexion in 24 of 72 knees. Conclusion: Reconstruction of the MPFL is a safe and effective treatment for patellofemoral instability without severe trochlear dysplasia and allows most patients to engage in regular sports activities 2 years postoperatively, at least at a recreational level. However, potential complications, such as persistent instability, pain, and loss of flexion, must be considered.

An exploratory double‐blind, randomized clinical trial with selisistat, a SirT1 inhibitor, in patients with Huntington's disease

AIMS Selisistat, a selective SirT1 inhibitor is being developed as a potentially disease-modifying therapeutic for Huntingtons disease (HD). This was the first study of selisistat in HD patients and was primarily aimed at development of pharmacodynamic biomarkers. METHODS This was a randomized, double-blind, placebo-controlled, multicentre exploratory study. Fifty-five male and female patients in early stage HD were randomized to receive 10 mg or 100 mg of selisistat or placebo once daily for 14 days. Blood sampling, clinical and safety assessments were conducted throughout the study. Candidate pharmacodynamic markers included circulating soluble huntingtin and innate immune markers. RESULTS Selisistat was found to be safe and well tolerated, and systemic exposure parameters showed that the average steady-state plasma concentration achieved at the 10 mg dose level (125 nm) was comparable with the IC50 for SirT1 inhibition. No adverse effects on motor, cognitive or functional readouts were recorded. While circulating levels of soluble huntingtin were not affected by selisistat in this study, the biological samples collected have allowed development of assay technology for use in future studies. No effects on innate immune markers were seen. CONCLUSIONS Selisistat was found to be safe and well tolerated in early stage HD patients at plasma concentrations within the anticipated therapeutic concentration range.

Global activation of primary motor cortex during voluntary movements in man.

Unilateral voluntary movements are accompanied by robust activation of contralateral primary motor cortex (M1) in a somatotopic fashion. Occasionally, coactivation of M1 (M1-CoA) ipsilateral to the movement was described. In a study with brain tumor patients, we consistently observed additional somatotopic M1-CoAs and hypothesized that they might represent a basic feature of movement execution. To test this hypothesis, we used BOLD functional magnetic resonance imaging in healthy subjects and show that unilateral voluntary movements of the fingers or toes go along not only with contralateral M1 activation, but also with ipsilateral M1-CoA of the respective homotopic representation and bilateral M1-CoA of different heterotopic representations not directly involved in the executed movement. Moreover, bilateral M1-CoA of heterotopic representations was observed in tongue movements. All M1-CoAs respected the correct somatotopy; however, their Euclidean coordinates were shifted and resembled to those obtained for imagined movements rather than for actual movements. BOLD signal intensities and correlations to the applied hemodynamic reference function were lower in M1-CoAs as compared to the M1 activations driving the movement but did not differ between homo- and heterotopic M1-CoAs. Thus, we propose that specific unilateral voluntary movements are accompanied by a global activation of primary motor areas, reflecting an overall increase in neuronal activity and unraveling the fundamental principle of distributed processing in M1. Executive motor function may rely on a balance of inhibitory and excitatory neuronal activity, where actual movement would result from a shift towards excitation.