Transgenic rat model of Huntington's disease

Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.     

Early recurrence of rheumatoid arthritis after nonmyeloablative allogeneic blood stem cell transplantation in a patient with multiple myeloma

Allogeneic blood stem cell transplantation with reduced conditioning has been proposed as a new, potentially curative treatment option for patients with rheumatoid arthritis (RA). We report a 60-year-old woman with RA and coexisting multiple myeloma who was treated with high-dose melphalan and autologous blood stem cell transplantation (BSCT) followed by a nonmyeloablative allogeneic BSCT from her healthy dizygotic twin brother. She achieved a complete remission of her RA after autologous BSCT, but relapsed early despite complete donor chimerism following successful allogeneic transplantation with reduced intensity conditioning. This case illustrates that allogeneic BSCT following nonmyeloablative conditioning may be an uncertain option for curing patients with RA.     

Neural response to emotional stimuli during experimental human endotoxemia

Increases in peripheral cytokines during acute inflammation may affect various neuropsychological functions. The aim of this functional magnetic resonance imaging (fMRI) study was to investigate the effects of acute endotoxemia on mood and the neural response to emotionally aversive visual stimuli in healthy human subjects. In a double‐blind, randomized crossover study, 18 healthy males received a bolus injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline. Plasma levels of pro‐ and anti‐inflammatory cytokines and cortisol as well as mood ratings were analyzed together with the blood‐oxygen‐level dependent (BOLD) response during the presentation of aversive versus neutral pictures. Endotoxin administration induced pronounced transient increases in plasma levels of TNF‐α, IL‐1ra, IL‐6, IL‐10, and cortisol. Positive mood was decreased and state anxiety increased. In addition, activation of right inferior orbitofrontal cortex (OFC) in response to emotional visual stimuli was significantly increased in the LPS condition. Increased prefrontal activation during the presentation of emotional material may reflect enhanced cognitive regulation of emotions as an adaptive response during an acute inflammation. These findings may have implications for the putative role of inflammatory processes in the pathophysiology of depression. Hum Brain Mapp 34:2217–2227, 2013. © 2012 Wiley Periodicals, Inc.     

Die Chronische Symphyseninstabilität

The most frequent causes of chronic instability of the pubic symphysis are sports-related continual overload and traumatic symphyseal injuries. Acute injury of the pubic symphysis may be the result of external forces acting on the anterior pelvic ring or the result of internal forces, such as those arising during parturition. The postpartum form of instability following a complication-free birth is reversible and usually returns to normal within a few months through strengthening of the pelvic floor muscles. Residual instability of the pubis symphysis is on the whole a rare complication. Although established therapy options for acute symphyseal separation can be found in the literature, there are only a few case reports on chronic symphyseal instability. There are no guidelines on standardized therapy options. This review article examines the etiology, clinical findings, diagnostic techniques and management options for patients suffering from chronic symphyseal instability.     

Does a pressure increase translate into an adjacent compartment? A cadaver study

Objectives

The influence of local pressure elevation on the adjacent compartment of the lower limb is poorly described. We examined these effects in a non-fractured cadaver model.

Methods

Paired legs of unfrozen specimens were used. The pressure in the anterior and in the peroneal compartment of the contralateral limb was raised by bolus injections of saline (5cc bolus/60 seconds. Pressure changes in the adjacent compartments were measured.

Results

Pressure increase in the anterior and peroneal compartment, up to 100 mmHg did not affect the mean maximum pressure changes in the other compartments. Exceeding 100 mmHg in the anterior compartment, the peroneal pressure was 13.67 mmHg(range 8–20 mmHg), the deep posterior 7.50 mmHg(5–13 mmHg) and the superficial compartment pressure was 6.67 mmHg(4–9 mmHg). In cases of raised pressures in the peroneal compartment above 100 mmHg, the anterior, deep and superficial posterior compartments showed pressures of 12.5 mmHg(11–15 mmHg), 7.5 mmHg(4–11 mmHg), and 7.5 mmHg(4–12 mmHg).

Conclusions

Our data suggest that increased pressures in the anterior tibial or peroneal compartments do not directly influence the neighbouring compartments. It appears that in an intact compartment, the fascia seals pressure elevations in the range that is clinically relevant. Whether or not this may have clinical impact on the indications for single versus multiple compartment fasciotomy should be subject to further studies.