Stimulation of the subthalamic nucleus at an earlier disease stage of Parkinson's disease: Concept and standards of the EARLYSTIM-study

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an established treatment for advanced Parkinson's disease (PD) with disabling motor complications. However, stimulation may be beneficial at an earlier stage of PD when motor fluctuations and dyskinesia are only mild and psychosocial competence is still maintained. The EARLYSTIM trial was conducted in patients with recent onset of levodopa-induced motor complications (≤3 years) whose social and occupational functioning remained preserved. This is called ‘early’ here. The study was a randomized, multicenter, bi–national pivotal trial with a 2 year observation period. Quality of life was the main outcome measure, and a video-based motor score was a blinded secondary outcome of the study. Motor, neuropsychological, psychiatric and psychosocial aspects were captured by established scales and questionnaires. The patient group randomized here is the earliest in the disease course and the youngest recruited in controlled DBS trials so far. The methodological innovation for DBS-studies of this study lies in novel procedures developed and used for monitoring best medical treatment, neurosurgical consistency, best management of stimulation programming, blinded video assessment of motor disability, and prevention of suicidal behaviors.     

Detection of Vertical Root Fractures in the Presence of Intracanal Metallic Post: A Comparison between Periapical Radiography and Cone-beam Computed Tomography

Introduction

This in vitro study compared cone-beam computed tomography (CBCT) exam with different voxel sizes with digital periapical radiography in the detection of vertical root fractures in teeth with and without intracanal metallic posts.

Methods

Eighteen single-rooted human teeth were endodontically treated, prepared for cast metal posts, and artificially fractured. After positioning the teeth in dry mandibular sockets, the samples were subjected twice (with and without posts) to digital periapical radiography at 3 different angles and to CBCT examinations with 2 voxel sizes, 0.125 and 0.25 mm. The images were evaluated by 3 oral radiologists. Indices of sensitivity, specificity, and positive and negative predictive values, in addition to the areas under the receiver operating characteristic curves (accuracy), were calculated. Comparison of the accuracy of the imaging methods was assessed by using the χ² test. Comparison of the accuracy between teeth with and without posts was determined by using the Fisher exact test.

Results

The accuracy of the imaging methods showed no significant differences (P = .08). The comparison between teeth with and without posts in each examination revealed significant differences for CBCT with a voxel of 0.125 mm (P = .04) and for periapical radiography (P = .04).

Conclusions

No significant differences were observed between CBCT and periapical radiography in the detection of vertical root fractures, except for teeth with metallic posts in images from CBCT with a voxel of 0.125 mm and in digital periapical radiography. Furthermore, voxel size did not significantly influence the diagnosis of vertical root fractures.     

History of non-fatal cardiovascular disease in a cohort of Dutch and British patients with haemophilia

Protein C (PC) deficiency is an autosomal dominant inherited disorder associated with spontaneous and recurrent thrombotic events. Factor V Leiden (FVL) increases the risk of thrombosis in PC-deficient type I families. We have investigated the relationship between PC deficiency genotype and clinical phenotype in a large four-degree Italian family followed since 1988. Methods: PC activity and antigen levels were quantified; sequencing of PC DNA was performed to identify polymorphism. FVL and factor II (G20210A) polymorphism were screened. Results: PC activity ranged from 5% to 9%, and PC antigen levels were 5,3% in two homozygous for PROC missense mutation Arg32Cys; PC activity ranged from 18% to 60% and antigen levels from 21% to 64%, respectively, in 11 heterozygous for Arg32Cys; PC activity was 99% and 120% in two wild type. Of 15, eight were heterozygous for FVL. The two subjects with PC < 6%, homozygous for Arg32Cys and heterozygous for FVL, suffered from thrombosis during childhood. Of 11, six subjects with PC deficiency and heterozygous for FVL showed the first thrombosis at an age between 21 and 54. None of the five PC-deficient subjects, who were wild type for FVL, showed thrombosis. Two subjects with PC > 70%, both heterozygous for FVL developed thrombosis in the presence of another risk factor. This study suggests that FVL and PROC mutations increase the risk of thrombosis in subjects with PC deficiency, which could be considered as a 'variable' risk factor. The thrombosis-prone PC-deficient families carry additional risk factors for thrombosis.     

Diabetes mellitus may increase bone loss after occlusal trauma and experimental periodontitis

Background: Diabetes mellitus (DM) involves metabolic changes that can negatively influence periodontal tissues, resulting in more prevalent and severe periodontitis and impaired bone formation. Occlusal trauma (OT) is an injury of the supportive periodontium that results in bone loss. It can be hypothesized that DM would increase bone loss after OT, mainly when associated with periodontitis. Thus, the aim of the present study is to evaluate the influence of DM on bone response in the furcation area of teeth subjected to OT in the presence, or absence, of experimental periodontitis (EP) in the rat model. Methods: Thirty-two male Wistar rats were assigned to four groups: 1) group 1 (G1): DM+OT+EP (n = 8); 2) group 2 (G2): DM+OT (n = 8); 3) group 3 (G3): OT+EP (n = 8); and 4) group 4 (G4): OT (n = 8). G1 and G2 received a single intraperitoneal injection of streptozotocin (STZ). After 10 days, G1 and G3 were subjected to EP by ligature placement. Fifteen days after the start of EP, OT was induced by the creation of a premature contact. The animals were euthanized 35 days after DM induction. Results: DM enhanced bone loss in the presence of OT combined with EP, but did not increase bone loss in teeth subjected to OT alone. EP caused greater bone loss when associated with OT. Conclusion: Within the limits of this animal study, it can be concluded that DM enhances bone loss in the presence of occlusal trauma associated with EP.     

The antioxidant tempol decreases acute pulmonary thromboembolism-induced hemolysis and nitric oxide consumption

Introduction

Acute pulmonary thromboembolism (APT) is a critical condition associated with acute pulmonary hypertension. Recent studies suggest that oxidative stress and hemolysis contribute to APT-induced pulmonary hypertension, possibly as a result of increased nitric oxide (NO) consumption. We hypothesized that the antioxidant tempol could attenuate APT-induced hemolysis, and therefore attenuate APT-induced increases in plasma NO consumption.

Materials and Methods

APT was induced in anesthetized sheep with autologous blood clots. The hemodynamic effects of tempol infused at 1.0 mg/kg/min 30 min after APT were determined. Hemodynamic measurements were carried out every 15 min. To assess oxidative stress, serum 8-isoprostanes levels were measured by ELISA. Plasma cell-free hemoglobin concentrations and NO consumption by plasma samples were determined. An in vitro oxidative AAPH-induced hemolysis assay was used to further validate the in vivo effects of tempol.

Results

APT caused pulmonary hypertension, and increased pulmonary vascular resistance in proportion with the increases in 8-isoprostanes, plasma cell-free hemoglobin concentrations, and NO consumption by plasma (all P < 0.05). Tempol attenuated the hemodynamic alterations by approximately 15-20% and blunted APT-induced increases in 8-isoprostanes, in cell-free hemoglobin concentrations, and the increases in NO consumption by plasma (P < 0.05). Tempol dose-dependently attenuated AAPH-induced in vitro hemolysis (P < 0.05).

Conclusions

Our findings are consistent with the idea that antioxidant properties of tempol decrease APT-induced hemolysis and nitric oxide consumption, thus attenuating APT-induced pulmonary hypertension.