Movement-related synchronization of gamma activity is lateralized in patients with dystonia

There is evidence for synchronization at frequencies both under 30 Hz and over 60-80 Hz in the so-called gamma frequency band in patients with Parkinson's disease (PD). Gamma activity increases after dopaminergic therapy and during voluntary movement, suggesting that it might be physiological and relate to motor processing in the basal ganglia (BG). We recorded local field potential (LFP) activity during a choice reaction time task in 11 patients with dystonia undergoing implantation of the internal globus pallidus for therapeutic stimulation. The spectral content of the LFP was averaged with respect to movement onset over 6-11 Hz, 18-25 Hz and 60-80 Hz, separately for responses ipsilateral and contralateral to movement. There was a perimovement increase in 60-80 Hz activity in the LFP, but only contralateral to movement. In contrast, low-frequency LFP activity decreased symmetrically during movement. This occurred earlier in the 18-25 Hz band than in the 6-11 Hz band, and was followed by a postmovement increase in oscillatory activity in the 18-25 Hz band that was contralateral to movement. The presence of a lateralized movement-related increase in gamma activity in the BG of patients with dystonia, similar to that recorded in patients with treated PD, suggests that this may be a residual feature of normal BG function. Moreover, the results provide further support for functional distinctions between BG oscillatory activities of different frequency.     

Morphologic changes in the vastus medialis muscle in patients with osteoarthritis of the knee

OBJECTIVE: To investigate the frequency of structural changes in the vastus medialis muscle in patients with osteoarthritis (OA) of the knee. METHODS: Specimens of vastus medialis muscle from 78 patients with end-stage OA of the knee undergoing total joint arthroplasty were examined histopathologically. Morphologic changes were assessed in relation to clinical features that might have contributed to muscle injury. RESULTS: All muscle specimens exhibited atrophy of type 2 fibers. In 32% of the patients, atrophy of type 1 fibers was also noted. Fiber type grouping of type 1 fiber in 15% of the patients and type 2 fiber in 37%, indicating reinnervation, led to the diagnosis of neurogenic muscular atrophy in 32% of the patients; selective atrophy of type 2 fiber in 68% of the specimens was interpreted as possibly resulting from pain-associated disuse. Signs of muscle degeneration and regeneration were found in 65% and 96% of the samples, respectively. Soft tissue changes indicating long-term disease, such as calcification, fibrosis, and lipomatosis, were frequently observed (in 69%, 71%, and 94% of the patients, respectively). Statistical analysis of clinical and morphologic parameters revealed a significant association between degenerative muscle changes and the presence of a varus deviation of the leg axis. CONCLUSION: Patients with OA of the knee frequently exhibit muscle changes, with probable multifactorial etiology. Selective atrophy of type 2 fibers might reflect pain-related immobilization of a limb. Changes such as neurogenic muscular atrophy, muscle fiber degeneration, and regeneration might contribute as cofactors in the development or progression of OA.     

A phase 2/3 multicenter randomized clinical trial of ABX-CBL versus ATG as secondary therapy for steroid-resistant acute graft-versus-host disease

Treatment for steroid-resistant acute graft-versus-host disease (GVHD) has had limited success. ABX-CBL is a hybridoma-generated murine IgM monoclonal antibody against the CD147 antigen, weakly expressed on human leukocytes and up-regulated on activated lymphocytes. A prospective, multicenter, open-label, randomized clinical trial comparing ABX-CBL to antithymocyte globulin (ATG) for treatment of steroid-resistant acute GVHD was conducted in 95 patients at 21 centers. Forty-eight patients received ABX-CBL daily for 14 consecutive days followed by up to 6 weeks of ABX-CBL twice weekly. Forty-seven patients received equine ATG, 30 mg/kg every other day for a total of 6 doses with additional courses as needed. By day 180, overall improvement was similar in the patients receiving ABX-CBL and in those receiving ATG (56% versus 57%, P = .91). Patient survival at 18 months was less favorable on ABX-CBL than on ATG (35% versus 45%), with the 95% confidence interval ruling out that ABX-CBL provides at least a 10.4% improvement. Data from this trial suggest that ABX-CBL does not offer an improvement over ATG in the treatment of acute steroid-resistant GVHD. This prospective, multicenter, randomized clinical trial for steroid-resistant acute GVHD serves as a model for future evaluation of new agents.     

Active breathing control (ABC): determination and reduction of breathing-induced organ motion in the chest

PURPOSE: Extensive radiotherapy volumes for tumors of the chest are partly caused by interfractional organ motion. We evaluated the feasibility of respiratory observation tools using the active breathing control (ABC) system and the effect on breathing cycle regularity and reproducibility. METHODS AND MATERIALS: Thirty-six patients with unresectable tumors of the chest were selected for evaluation of the ABC system. Computed tomography scans were performed at various respiratory phases starting at the same couch position without patient movement. Threshold levels were set at minimum and maximum volume during normal breathing cycles and at a volume defined as shallow breathing, reflecting the subjective maximal tolerable reduction of breath volume. To evaluate the extent of organ movement, 13 landmarks were considering using commercial software for image coregistration. In 4 patients, second examinations were performed during therapy. RESULTS: Investigating the differences in a normal breathing cycle versus shallow breathing, a statistically significant reduction of respiratory motion in the upper, middle, and lower regions of the chest could be detected, representing potential movement reduction achieved through reduced breath volume. Evaluating interfraction reproducibility, the mean displacement ranged between 0.24 mm (chest wall/tracheal bifurcation) to 3.5 mm (diaphragm) for expiration and shallow breathing and 0.24 mm (chest wall) to 5.25 mm (diaphragm) for normal inspiration. CONCLUSIONS: By modifying regularity of the respiratory cycle through reduction of breath volume, a significant and reproducible reduction of chest and diaphragm motion is possible, enabling reduction of treatment planning margins.     

A population-based study of survival in patients with secondary myelodysplastic syndromes (MDS): impact of type and treatment of primary cancers

Objective Myelodysplastic syndromes (MDS) following treatment with chemotherapy or irradiation are termed ‘secondary’ MDS. Clinical observations suggest a worse prognosis for secondary than for primary MDS, but differences in survival have not been studied in a general population sample. Methods We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) program to describe survival in MDS patients according to previous cancer diagnosis. Our study included 3,938 MDS cases diagnosed in 2001–2004 and reported by registries which have participated in SEER since the 1970s. Results A previous cancer diagnosis (26% of MDS cases) was associated with 13% increased risk of death from any cause among MDS cases (hazard ratio [HR]=1.13, 95% confidence interval [CI]: 1.02–1.25). Radiation treatment for a previous cancer was associated with 52% increased risk of death (95% CI: 1.15–2.02). Shortened survival was most pronounced if the latency between the previous cancer and MDS was less than five years, including lung cancer diagnosed in the year preceding MDS (HR = 3.43, 95% CI: 1.93–6.10) and lymphohematopoietic cancer 1–5 years before MDS (HR = 2.11; 95% CI: 1.33–3.36). Conclusions Our results confirm a more severe prognosis for secondary MDS than for primary MDS, associated with certain types and treatments of previous cancer. Financial support: Dr. De Roos’ and Dr. Davis’ work was supported by a grant from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute (NO1-PC-55020-20), and Dr. Deeg’s work was supported by grants from the National Heart, Lung, and Blood Institute of the National Institutes of Health (HL36444 and HL082941).