Effect of Zoledronic Acid on Acro-Osteolysis and Osteoporosis in a Patient with Hajdu-Cheney Syndrome

Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself

Isometric muscle training of the spine musculature in patients with spinal bony metastases under radiation therapy

<p/> <p>Background</p> <p>Osseous metastatic involvement of the spinal column affects many patients with a primary tumour disease of all entities. The consequences are pain both at rest and under exertion, impairments in going about day-to-day activities, diminished performance, the risk of pathological fractures, and neurological deficits. Palliative percutaneous radiotherapy is one of the therapeutical options available in this connection. The aim of this explorative study is to investigate the feasibility of muscle-training exercises and to evaluate the progression- and fracture-free survival time and the improvement of bone density, as well as to assess other clinical parameters such as pain, quality of life, and fatigue as secondary endpoints.</p> <p>Methods/Design</p> <p>This study is a prospective, randomized, monocentre, controlled explorative intervention study in the parallel-group design to determine the multidimensional effects of a course of exercises at first under physiotherapeutic instruction and subsequently performed by the patients independently for strengthening the paravertebral muscles of patients with metastases of the vertebral column parallel to their percutaneous radiotherapy. On the days of radiation treatment the patients in the control group shall be given physical treatment in the form of respiratory therapy and the so-called "hot roll". The patients will be randomized into one of the two groups: differentiated muscle training or physiotherapy with thirty patients in each group.</p> <p>Discussion</p> <p>The aim of the study is to evaluate the feasibility of the training programme described here. Progression-free and fracture-free survival, improved response to radiotherapy by means of bone density, and clinical parameters such as pain, quality of life, and fatigue constitute secondary study objectives.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01409720">NCT01409720</a></p

Radial shortening following a fracture of the proximal radius: Degree of shortening and short-term outcome in 22 proximal radial fractures

Background and purpose: The Essex-Lopresti lesion is thought to be rare, with a varying degree of disruption to forearm stability probable. We describe the range of radial shortening that occurs following a fracture of the proximal radius, as well as the short-term outcome in these patients. Patients and methods Over an 18-month period, we prospectively assessed all patients with a radiographically confirmed proximal radial fracture. Patients noted to have ipsilateral wrist pain at initial presentation underwent bilateral radiography to determine whether there was disruption of the distal radio-ulnar joint suggestive of an Essex-Lopresti lesion. Outcome was assessed after a mean of 6 (1.5-12) months using clinical and radiographic results, including the Mayo elbow score (MES) and the short musculoskeletal function assessment (SMFA) questionnaire. One patient with a Mason type-I fracture was lost to follow-up after initial presentation. Results 60 patients had ipsilateral wrist pain at the initial assessment of 237 proximal radial fractures. Radial shortening of ≥ 2mm (range: 2-4mm) was seen in 22 patients (mean age 48 (19-79) years, 16 females). The most frequent mechanism of injury was a fall from standing height (10/22). 21 fractures were classified as being Mason type-I or type-II, all of which were managed nonoperatively. One Mason type-III fracture underwent acute radial head replacement. Functional outcome was assessed in 21 patients. We found an excellent or good MES in 18 of the 20 patients with a Mason type-I or type-II injury. Interpretation The incidence of the Essex-Lopresti lesion type is possibly under-reported as there is a spectrum of injuries, and subtle disruptions often go unidentified. A full assessment of all patients with a proximal radial fracture is required in order to identify these injuries, and the index of suspicion is raised as the complexity of the fracture increases.</p

Procollagen Triple Helix Assembly: An Unconventional Chaperone-Assisted Folding Paradigm

Fibers composed of type I collagen triple helices form the organic scaffold of bone and many other tissues, yet the energetically preferred conformation of type I collagen at body temperature is a random coil. In fibers, the triple helix is stabilized by neighbors, but how does it fold? The observations reported here reveal surprising features that may represent a new paradigm for folding of marginally stable proteins. We find that human procollagen triple helix spontaneously folds into its native conformation at 30–34°C but not at higher temperatures, even in an environment emulating Endoplasmic Reticulum (ER). ER-like molecular crowding by nonspecific proteins does not affect triple helix folding or aggregation of unfolded chains. Common ER chaperones may prevent aggregation and misfolding of procollagen C-propeptide in their traditional role of binding unfolded polypeptide chains. However, such binding only further destabilizes the triple helix. We argue that folding of the triple helix requires stabilization by preferential binding of chaperones to its folded, native conformation. Based on the triple helix folding temperature measured here and published binding constants, we deduce that HSP47 is likely to do just that. It takes over 20 HSP47 molecules to stabilize a single triple helix at body temperature. The required 50–200 µM concentration of free HSP47 is not unusual for heat-shock chaperones in ER, but it is 100 times higher than used in reported in vitro experiments, which did not reveal such stabilization

Caribbean-wide decline in carbonate production threatens coral reef growth

This a post-print, author-produced version of an article accepted for publication in Nature Communications. Copyright © 2013 Nature Publishing Group . The definitive version is available at http://www.nature.com/ncomms/journal/v4/n1/full/ncomms2409.htmlGlobal-scale deteriorations in coral reef health have caused major shifts in species composition. One projected consequence is a lowering of reef carbonate production rates, potentially impairing reef growth, compromising ecosystem functionality and ultimately leading to net reef erosion. Here, using measures of gross and net carbonate production and erosion from 19 Caribbean reefs, we show that contemporary carbonate production rates are now substantially below historical (mid- to late-Holocene) values. On average, current production rates are reduced by at least 50%, and 37% of surveyed sites were net erosional. Calculated accretion rates (mm year(-1)) for shallow fore-reef habitats are also close to an order of magnitude lower than Holocene averages. A live coral cover threshold of ~10% appears critical to maintaining positive production states. Below this ecological threshold carbonate budgets typically become net negative and threaten reef accretion. Collectively, these data suggest that recent ecological declines are now suppressing Caribbean reef growth potential

Acute fibrinolysis shutdown occurs early in septic shock and is associated with increased morbidity and mortality: results of an observational pilot study

Background: Septic coagulopathy represents a very dynamic disease entity, tilting from initial hypercoagulability towards a subsequent hypocoagulable disease state, entitled overt disseminated intravascular coagulation. Acute fibrinolysis shutdown has recently been described to be a crucial component of initial hypercoagulability in critically ill patients, although the underlying pathomechanisms, the specific temporal kinetics and its outcome relevance in patients with sepsis remain to be determined. Methods: In total, 90 patients (30 with septic shock, 30 surgical controls and 30 healthy volunteers) were enrolled. Blood samples were collected at sepsis onset or prior and immediately after the surgical procedure as well as 3 h, 6 h, 12 h, 24 h, 48 h and 7 d later, whereas blood samples from healthy volunteers were collected once. Besides viscoelastic and aggregometric point-of-care testing (POCT), enzyme-linked immunosorbent and thrombin generation assays and liquid chromatography–mass spectrometry-based measurements were performed. Results: As assessed by viscoelastic POCT, fibrinolysis shutdown occurred early in sepsis. Significant increases in tissue plasminogen activator had no effect on thromboelastometrical lysis indices (LIs). Contrariwise, plasminogen activator inhibitor-1 was already significantly increased at sepsis onset, which was paralleled by significantly increased LIs in patients suffering from septic shock in comparison with both control groups. This effect persisted throughout the 7-day observation period and was most pronounced in severely ill as well as non-surviving septic patients. Thromboelastometrical LI, therefore, proved to be suitable for early diagnosis [e.g. LI 45 min: area under the curve (AUC) up to 0.933] as well as prognosis (e.g. LI 60 min: AUC up to 1.000) of septic shock. Conclusions: Early inhibition of plasminogen activation leads to acute fibrinolysis shutdown with improved clot stability and is associated with increased morbidity and mortality in septic patients. Trial registration This study was approved by the local ethics committee (Ethics Committee of the Medical Faculty of Heidelberg; Trial-Code No. S247-2014/German Clinical Trials Register (DRKS)-ID: DRKS00008090; retrospectively registered: 07.05.2015). All study patients or their legal representatives signed written informed consent