An in vivo study of a growth-factor enhanced, cell free, two-layered collagen-tricalcium phosphate in deep osteochondral defects

Focal osteochondral defects are still a challenging problem in joint surgery. We have developed a two-layered implant consisting of a basal porous beta-tricalcium phosphate (TCP) for bone reconstruction and a superficial fibrous collagen type I/III layer for cartilage regeneration. Fifty-four osteochondral defects in the trochlear groove of 27 Göttinger Minipigs were created and either left untreated, treated with the implant alone, or the implant augmented with an additional growth factor mixture, which was assumed to stimulate cell and tissue differentiation. Follow-up was 6, 12 and 52 weeks with n=6 for each group. The repair tissue was evaluated for its gross appearance and biomechanical properties. Histological sections were semi-quantitatively scored for their histomorphological structure. Treatment with the two-layered implant improved defect filling and subchondral bone repair at 6 and 12 weeks follow-up. The TCP was replaced by cancellous bone at 52 weeks. Cartilage repair tissue mainly consisted of fibrocartilage and showed a moderate cell density up to the joint surface. Growth factor treatment improved the mechanical and histomorphological properties of the cartilage repair tissue at 12, but not at 52 weeks postoperatively. In conclusion, the two-layered collagen-TCP implant augmented with chondroinductive growth factors seems a promising new option for the treatment of deep osteochondral defects in joint surgery.

Stenting of common iliac vein obstructions combined with regional thrombolysis and thrombectomy in acute deep vein thrombosis

OBJECTIVES: To evaluate the efficacy of stent placement after infrainguinal loco-regional thrombolysis and iliac thrombectomy (surgical TT) of acute deep vein thrombosis (DVT) in patients with May-Thurner-Syndrome. MATERIAL AND METHODS: We retrospectively analysed a group of 11 patients (9 women) (mean age 34 years, range 16-64 years) with surgical TT and additional intra-operative stenting due to compression of the common iliac vein. Patients underwent venography to demonstrate outflow patency after surgical TT, and to identify any obstruction at the level of the left-sided common iliac vein ("Beckenvenen-Sporn"). Obstruction at the level of arterial crossing was treated using Wallstents placed via an introducer sheath from the inguinal access site. Stents were fully deployed using balloons adjusted to the size of vein. Patients were treated with oral anticoagulants for 6 months, and followed using duplex ultrasonography. RESULTS: Technical success defined as complete vein patency and normal valve function was documented in all 11 patients. One patient needed early stent extension due to residual stenosis. At 6 months follow-up one patient (9%) had an asymptomatic occlusion of the stented common iliac vein. In all 11/11 (100%) patients the femoral segment was found to be patent, and in 1/11 (9%) there was mild reflux with few clinical symptoms of post-thrombotic syndrome. The calculated cumulative primary patency rate for venous iliac stents was 82%, and assisted patency rate was 91%, which remained unchanged over a mean follow-up of 22 months. CONCLUSION: Combining surgical TT and stenting of common iliac vein obstructions in DVT is safe, effective, and results in a acceptable venous patency.

EDML1: a chronology for the EPICA deep ice core from Dronning Maud Land, Antarctica, over the last 150 000 years

A chronology called EDML1 has been developed for the EPICA ice core from Dronning Maud Land (EDML). EDML1 is closely interlinked with EDC3, the new chronology for the EPICA ice core from Dome-C (EDC) through a stratigraphic match between EDML and EDC that consists of 322 volcanic match points over the last 128 ka. The EDC3 chronology comprises a glaciological model at EDC, which is constrained and later selectively tuned using primary dating information from EDC as well as from EDML, the latter being transferred using the tight stratigraphic link between the two cores. Finally, EDML1 was built by exporting EDC3 to EDML. For ages younger than 41 ka BP the new synchronized time scale EDML1/EDC3 is based on dated volcanic events and on a match to the Greenlandic ice core chronology GICC05 via 10Be and methane. The internal consistency between EDML1 and EDC3 is estimated to be typically ~6 years and always less than 450 years over the last 128 ka (always less than 130 years over the last 60 ka), which reflects an unprecedented synchrony of time scales. EDML1 ends at 150 ka BP (2417 m depth) because the match between EDML and EDC becomes ambiguous further down. This hints at a complex ice flow history for the deepest 350 m of the EDML ice core.

Mechanisms contributing to the deep chlorophyll maximum in Lake Superior

The seasonal appearance of a deep chlorophyll maximum (DCM) in Lake Superior is a striking phenomenon that is widely observed; however its mechanisms of formation and maintenance are not well understood. As this phenomenon may be the reflection of an ecological driver, or a driver itself, a lack of understanding its driving forces limits the ability to accurately predict and manage changes in this ecosystem. Key mechanisms generally associated with DCM dynamics (i.e. ecological, physiological and physical phenomena) are examined individually and in concert to establish their role. First the prevailing paradigm, “the DCM is a great place to live”, is analyzed through an integration of the results of laboratory experiments and field measurements. The analysis indicates that growth at this depth is severely restricted and thus not able to explain the full magnitude of this phenomenon. Additional contributing mechanisms like photoadaptation, settling and grazing are reviewed with a one-dimensional mathematical model of chlorophyll and particulate organic carbon. Settling has the strongest impact on the formation and maintenance of the DCM, transporting biomass to the metalimnion and resulting in the accumulation of algae, i.e. a peak in the particulate organic carbon profile. Subsequently, shade adaptation becomes manifest as a chlorophyll maximum deeper in the water column where light conditions particularly favor the process. Shade adaptation mediates the magnitude, shape and vertical position of the chlorophyll peak. Growth at DCM depth shows only a marginal contribution, while grazing has an adverse effect on the extent of the DCM. The observed separation of the carbon biomass and chlorophyll maximum should caution scientists to equate the DCM with a large nutrient pool that is available to higher trophic levels. The ecological significance of the DCM should not be separated from the underlying carbon dynamics. When evaluated in its entirety, the DCM becomes the projected image of a structure that remains elusive to measure but represents the foundation of all higher trophic levels. These results also offer guidance in examine ecosystem perturbations such as climate change. For example, warming would be expected to prolong the period of thermal stratification, extending the late summer period of suboptimal (phosphorus-limited) growth and attendant transport of phytoplankton to the metalimnion. This reduction in epilimnetic algal production would decrease the supply of algae to the metalimnion, possibly reducing the supply of prey to the grazer community. This work demonstrates the value of modeling to challenge and advance our understanding of ecosystem dynamics, steps vital to reliable testing of management alternatives.

Long-term pallidal deep brain stimulation in patients with advanced Parkinson disease: 1-year follow-up study

OBJECT: The goal of this study was to investigate the efficacy of long-term deep brain stimulation (DBS) of the posteroventral lateral globus pallidus internus (GPi) accomplished using a single-contact monopolar electrode in patients with advanced Parkinson disease (PD). METHODS: Sixteen patients suffering from severe PD and levodopa-induced side effects such as dyskinesias and on-off fluctuations were enrolled in a prospective study protocol. There were six women and 10 men and their mean age at surgery was 65 years. All patients underwent implantation of a monopolar electrode in the posteroventral lateral GPi. Initially, nine patients received unilateral stimulation. Three of these patients underwent contralateral surgery at a later time. Ten patients received bilateral stimulation (contemporaneous bilateral surgery was performed in seven patients and staged bilateral surgery in the three patients who had received unilateral stimulation initially). Formal assessments were performed during both off-medication and on-medication (levodopa) periods preoperatively, and at 3 and 12 months postoperatively. There were no serious complications related to surgery or to DBS. Two transient adverse events occurred: in one patient a small pallidal hematoma developed, resulting in a prolonged micropallidotomy effect, and in another patient a subcutaneous hemorrhage occurred at the site of the pacemaker. In patients who received unilateral DBS, the Unified Parkinson's Disease Rating Scale activities of daily living (ADL) score during the off-levodopa period decreased from 30.8 at baseline to 20.4 at 3 months (34% improvement) and 20.6 at 12 months (33% improvement) postoperatively. The motor score during the off period improved from 57.2 at baseline to 35.2 at 3 months (38% improvement) and 35.3 at 12 months (38% improvement) postoperatively. Bilateral DBS resulted in a reduction in the ADL score during the off period from 34.9 at baseline to 22.3 at 3 months (36% improvement) and 22.9 at 12 months (34% improvement). The motor score for the off period changed from 63.4 at baseline to 40.3 at 3 months (36% improvement) and 37.5 at 12 months (41% improvement). In addition, there were significant improvements in patients' symptoms during the on period and in on-off motor fluctuations. CONCLUSIONS: Pallidal DBS accomplished using a monopolar electrode is a safe and effective procedure for treatment of advanced PD. Compared with pallidotomy, the advantages of pallidal DBS lie in its reversibility and the option to perform bilateral surgery in one session. Comparative studies in which DBS is applied to other targets are needed.

Deep brain stimulation for dystonia: outcome at long-term follow-up

OBJECTIVE: Deep brain stimulation (DBS) has emerged as a useful therapeutic option for patients with insufficient benefit from conservative treatment. METHODS: Nine patients with chronic DBS who suffered from cervical dystonia (4), generalized dystonia (2), hemidystonia (1), paroxysmal dystonia (1) and Meige syndrome (1) were available for formal follow-up at three years postoperatively, and beyond up to 10 years. All patients had undergone pallidal stimulation except one patient with paroxysmal dystonia who underwent thalamic stimulation. RESULTS: Maintained improvement was seen in all patients with pallidal stimulation up to 10 years after surgery except in one patient who had a relative loss of benefit in dystonia ratings but continued to have improved disability scores. After nine years of chronic thalamic stimulation there was a mild loss of efficacy which was regained when the target was changed to the pallidum in the patient with paroxysmal dystonia. There were no major complications related to surgery or to chronic stimulation. Pacemakers had to be replaced within 1.5 to 2 years, in general. CONCLUSION: DBS maintains marked long-term symptomatic and functional improvement in the majority of patients with dystonia.