Spontaneous and reversible self-assembly of a polypeptide fragment of insulin-like growth factor binding protein-2 into fluorescent nanotubular structures

In this communication, we report the spontaneous and reversible in vitro self-assembly of a polypeptide fragment derived from the C-terminal domain of Insulin-like Growth Factor Binding Protein (IGFBP-2) into soluble nanotubular structures several micrometres long via a mechanism involving inter-molecular disulfide bonds and exhibiting enhanced fluorescence.

Fatigue fractures in military conscripts : A study on risk factors, diagnostics and long-term consequences

Fatigue fracture is an overuse injury commonly encountered in military and sports medicine, and known to relate to intensive or recently intensified physical activity. Bone responds to increased stress by enhanced remodeling. If physical stress exceeds bone s capability to remodel, accumulation of microfractures can lead to bone fatigue and stress fracture. Clinical diagnosis of stress fractures is complex and based on patient s anamnesis and radiological imaging. Bone stress fractures are mostly low-risk injuries, healing well after non-operative management, yet, occurring in high-risk areas, stress fractures can progress to displacement, often necessitating surgical treatment and resulting in prolonged morbidity. In the current study, the role of vitamin D as a predisposing factor for fatigue fractures was assessed using serum 25OHD level as the index. The average serum 25OHD concentration was significantly lower in conscripts with fatigue fracture than in controls. Evaluating TRACP-5b bone resorption marker as indicator of fatigue fractures, patients with elevated serum TRACP-5b levels had eight times higher probability of sustaining a stress fracture than controls. Among the 154 patients with exercise induced anterior lower leg pain and no previous findings on plain radiography, MRI revealed a total of 143 bone stress injuries in 86 patients. In 99% of the cases, injuries were in the tibia, 57% in the distal third of the tibial shaft. In patients with injury, forty-nine (57%) patients exhibited bilateral stress injuries. In a 20-year follow-up, the incidence of femoral neck fatigue fractures prior to the Finnish Defence Forces new regimen in 1986 addressing prevention of these fractures was 20.8/100,000, but rose to 53.2/100,000 afterwards, a significant 2.6-fold increase. In nineteen subjects with displaced femoral neck fatigue fractures, ten early local complications (in first postoperative year) were evident, and after the first postoperative year, osteonecrosis of the femoral head in six and osteoarthritis of the hip in thirteen patients were found. It seems likely that low vitamin D levels are related to fatigue fractures, and that an increasing trend exists between TRACP-5b bone resorption marker elevation and fatigue fracture incidence. Though seldom detected by plain radiography, fatigue fractures often underlie unclear lower leg stress-related pain occurring in the distal parts of the tibia. Femoral neck fatigue fractures, when displaced, lead to long-term morbidity in a high percentage of patients, whereas, when non-displaced, they do not predispose patients to subsequent adverse complications. Importantly, an educational intervention can diminish the incidence of fracture displacement by enhancing awareness and providing instructions for earlier diagnosis of fatigue fractures.

Primary Dislocation of the Patella : A Clinical Study

A total of 177 patients with primary dislocation of the patella (PDP) were admitted to two trauma centers in Helsinki, Finland during 1991 to 1992. The inclusion criteria were: 1. Acute (≤14 days old) first-time lateral dislocation of the patella. 2. No previous knee operations or major knee injuries. 3. No ligament injuries to be repaired. 4. No osteochondral fractures requiring fixation. 50 patients were excluded. 30 of these excluded patients would have met the inclusion criteria, 19 patients received treatment by consultants not involved in the study, 7 refused to participate and 4 had an erroneous randomization. 127 patients including, 82 females, were then randomized to have either tailor-made operative procedure (group O) or conservative treatment (group C). The aftercare was similar for both groups. The mean age of the patients was 20 (9-47) years. All patients were subjected to analysis of trauma history (starting position and knee movement during the dislocation), examination under anesthesia (EUA) and arthroscopy. 70 patients (52 females) were randomized by their odd year of birth to operative group O and 57 patients (30 females) by their even year of birth to conservative group C. The diagnosis of PDP was based on locked dislocation in 68 patients, on dislocatability in EUA in 47 patients, and on subluxation in EUA combined with typical intra-articular lesions in 12 patients. In group O, 63 patients had exploration of the injuries on the medial side of the knee and tailor made reconstruction added with lateral release in 54 cases. The medial injury was operated by suturing in 39 patients, by duplication in 18 patients and by additional augmentation of the medial patellofemoral ligament (MPFL) with adductor magnus tenodesis in 6 patients. 7 patients, without locking in trauma history and only subluxation in EUA had only lateral release for realignment. In adductor magnus tenodesis the proximal end of the distal tendinous part was rerouted to the upper medial border of the patella. In the conservative group C, the treatment was adjusted to the extent of patellar displacement in EUA. Patients with dislocation in EUA had 3 weeks’ immobilization with the knee in slight flexion. Mobilization was started with a soft patellar stabilizing orthosis (PSO) used for additional three weeks. The patients with subluxation in EUA wore an orthosis for six weeks. The aftercare was similar in group O. The outcome was similar in both groups. After an average of 25 (20-45) months´ follow-up, the subjective result was better in group C in respect of the mean Hughston VAS knee score (87 for group O and 90 for group C, p=0.04, visual analog scale), but similar in terms of the patient’s own overall opinion and the mean Lysholm II knee score. Recurrent instability episodes occurred in 18 patients in group O and in 20 patients in group C. After an average of 7 (6-9) years´ follow-up, the groups did not show statistical difference either in respect of the patient’s own overall opinion, or the mean Hughston VAS and Kujala knee scores. The proportions of stable patellae was 25/70 (36%) in group O and 17/57 (30%) in group O (p=0.5). In a multivariate risk analysis, there was a correlation between low Kujala score (<90) as dependent parameter and female gender (OR: 3.5; 95% CI: 1.4-9.0), and loose body on primary radiographs (OR: 4.1; 95% CI: 1.2-15). Recurrent instability correlated with young age at the time of PDP (OR: 0.9; 95% CI: 0.8-1.0/year). Girls with open tibial apophysis had the worst prognosis for instability (88%; 95% CI: 77-98). The most common mechanisms in trauma history of the patients were movement to flexion from a straight start (78%) and movement to extension from a well-bent start (8%). Spontaneous relocation of the patella had taken place in 13/39 of girls, in 11/21 of boys, in 26/42 of women and in 17/24 of men with skeletal maturity of the tibia. The dislocation in EUA was non-rotating in 96/126 patients followed by outward rotating dislocation in 14/126 patients. Operative treatment policy in PDP is not recommended. Locking tendency of the patella in PDP depended on the skeletal maturation. Recurrence rate after PDP was higher than expected.

Imaging of knee injuries with special focus on tibial plateau fractures

Acute knee injury is a common event throughout life, and it is usually the result of a traffic accident, simple fall, or twisting injury. Over 90% of patients with acute knee injury undergo radiography. An overlooked fracture or delayed diagnosis can lead to poor patient outcome. The major aim of this thesis was retrospectively to study imaging of knee injury with a special focus on tibial plateau fractures in patients referred to a level-one trauma center. Multi-detector computed tomography (MDCT) findings of acute knee trauma were studied and compared to radiography, as well as whether non-contrast MDCT can detect cruciate ligaments with reasonable accuracy. The prevalence, type, and location of meniscal injuries in magnetic resonance imaging (MRI) were evaluated, particularly in order to assess the prevalence of unstable meniscal tears in acute knee trauma with tibial plateau fractures. The possibility to analyze with conventional MRI the signal appearance of menisci repaired with bioabsorbable arrows was also studied. The postoperative use of MDCT was studied in surgically treated tibial plateau fractures: to establish the frequency and indications of MDCT and to assess the common findings and their clinical impact in a level-one trauma hospital. This thesis focused on MDCT and MRI of knee injuries, and radiographs were analyzed when applica-ble. Radiography constitutes the basis for imaging acute knee injury, but MDCT can yield information beyond the capabilities of radiography. Especially in severely injured patients , sufficient radiographs are often difficult to obtain, and in those patients, radiography is unreliable to rule out fractures. MDCT detected intact cruciate ligaments with good specificity, accuracy, and negative predictive value, but the assessment of torn ligaments was unreliable. A total of 36% (14/39) patients with tibial plateau fracture had an unstable meniscal tear in MRI. When a meniscal tear is properly detected preoperatively, treatment can be combined with primary fracture fixation, thus avoiding another operation. The number of meniscal contusions was high. Awareness of the imaging features of this meniscal abnormality can help radiologists increase specificity by avoiding false-positive findings in meniscal tears. Postoperative menisci treated with bioabsorbable arrows showed no difference, among different signal intensities in MRI, among menisci between patients with operated or intact ACL. The highest incidence of menisci with an increased signal intensity extending to the meniscal surface was in patients whose surgery was within the previous 18 months. The results may indicate that a rather long time is necessary for menisci to heal completely after arrow repair. Whether the menisci with an increased signal intensity extending to the meniscal surface represent improper healing or re-tear, or whether this is just the earlier healing feature in the natural process remains unclear, and further prospective studies are needed to clarify this. Postoperative use of MDCT in tibial plateau fractures was rather infrequent even in this large trauma center, but when performed, it revealed clinically significant information, thus benefitting patients in regard to treatment.

Consequences of Vertebral Fractures

Vertebral fractures occur due to forces applied to spinal structures. When the bone tissue is weakened, vertebral fractures can result from a minor trauma. Adult vertebral fractures are commonly considered to be an indication for osteoporosis. In children osteoporosis is a rare condition, and pediatric vertebral fractures are usually clearly trauma-related. The aims of this dissertation are to produce knowledge of the epidemiology of osteoporotic vertebral fractures and to analyse their association with total and cause-specific mortality, to find indicators with which to identify individuals who are at great risk of subsequent fractures, to study the incidence of pediatric vertebral fractures and need for their operative treatment and hospital care. The Mobile-Clinic and Mini-Finland Health surveys of the adult population were used as materials in this research. Record linkages to the Finnish Hospital Discharge Register and the Official Cause of Death register were used to study mortality and hospitalization in the same population group. These registers were also used to evaluate epidemiology, mortality, hospitalization and the need for operative management of pediatric vertebral fracture patients. The main findings and conclusions of the present dissertation are: 1. The presence of a thoracic vertebral fracture in adults is a significant predictor of cancer and respiratory mortality. In women, but not in men, vertebral fractures strongly predict mortality due to injuries. Most of these deaths in the study group were hip fracture related. 2. Severe thoracic vertebral fracture in adults was a strong predictor of a subsequent hip fracture, whereas mild or moderate fractures and the number of compressed vertebrae were much weaker predictors, 3. Pediatric spinal fractures were rare: The incidence was 66 per one million children per year. In younger children cervical spine was most often affected, whereas in older children fractures of the thoracic and lumbar spine were more common. Maturation of spinal structures seems to play a major role in the typical injury patterns in children. Thirty per cent of pediatric spinal fractures required surgical treatment. The current study focuses on consequences of vertebral fractures in general, without evaluating further the causation of the studied phenomena. Further studies are needed to clarify the mechanisms of association between vertebral fractures and specific causes of mortality. A severe vertebral fracture appears to indicate a substantial risk of a subsequent hip fracture. If such a fracture is identified from a chest radiograph, urgent clinical evaluation, treatment of osteoporosis and protective measures against falls are recommended.

Generation of Cationic Two-Coordinate Group-13 Ligand Systems by Spontaneous Halide Ejection: Remarkably Nucleophile-Resistant (Dimethylamino)borylene Complexes

Spontaneous ejection of chloride from a three-coordinate boron Lewis acid can be effected by employing very electron rich metal substituents and leads to the formation of a sterically unprotected terminal (dimethylamino)borylene complex that has a short metal-boron bond and remarkable resistance to attack by nucleophilic and protic reagents.

(Dimethylamino)borylene and Related Complexes of Electron-Rich Metal Fragments: Generation of Nucleophile-Resistant Cations by Spontaneous Halide Ejection

Spontaneous halide ejection from a three-coordinate Lewis acid has been shown to offer a remarkable new route to cationic metal complexes featuring a linear, multiply bonded boron-donor Ligand. The exploitation of electron-rich [CpM(PR3)(2)] fragments within boryl systems of the type LnMB(hal)NR2 leads to the spontaneous formation in polar solvents of chemically robust borylene complexes, [LnM(BNR2)](+), with exceptionally low electrophilicity and short M-B bonds. This is reflected by M-B distances (ca. 1.80 angstrom for FeB systems) which are more akin to alkyl-/aryl-substituted borylene complexes and, perhaps most strikingly, by the very low exothermicity associated with the binding of pyridine to the two-coordinate boron center (Delta H = -7.4 kcal mol(-1), cf. -40.7 kcal mol(-1) for BCl3). Despite the strong pi electron release from the metal fragment implied by this suppressed reactivity and by such short M-B bonds, the barrier to rotation about the Fe=B bond in the unsymmetrical variant [CpFe(dmpe)(BN{C6H4OMe-4}Me)](+) is found to be very small (ca. 2.9 kcal mol(-1)). This apparent contradiction is rationalized by the orthogonal orientations of the HOMO and HOMO-2 orbitals of the [CpML2](+) fragment, which mean that the M-B pi interaction does not fall to zero even in the highest energy conformation.