Fully state-selected VMI study of the near-threshold photodissociation of NO(2): variation of the angular anisotropy parameter.

Velocity-map ion imaging (VMI) has been used to study the angular distribution of the NO fragment generated in the photodissociation of NO(2) at a variety of photolysis wavelengths. Images were recorded for the channels NO (2)Pi(1/2) (v = 0, J= 3/2, 11/2 and 21/2) + O ((3)P(2,1)), for excitation energies ranging from the onset (E(avl)/hc = 0 cm(-1)) to E(avl)/hc approximately 900 cm(-1). The angular anisotropy parameter beta was obtained as a function of available energy. Photofragment multiphoton ionization (PHOMPI) spectra were also recorded in the energy range E(avl)/hc = 0-300 cm(-1) for each of these channels. Large fluctuations of beta as a function of E(avl) were found in all observed dissociation channels. These variations are discussed in terms of the lifetimes of the originally photoexcited overlapping resonances in the A(2)B(2) state of NO(2), the dynamics of which are strongly influenced by nonadiabatic coupling with the X[combining tilde](2)A(1) state. The potential use of this photolysis process for production of cold oxygen atoms is discussed.

High-level bacterial expression and purification of apicomplexan micronemal proteins for structural studies.

The cysteine-rich N-terminal domain of the micronemal adhesive protein MIC1 (MIC1-NT) from Toxoplasma gondii was cloned, expressed in Escherichia coli and purified. MIC1-NT is amenable to structural studies as shown by preliminary NMR and X-ray analysis. Positive results with two further micronemal proteins indicate that our strategy has wider application.

Application of recombinant BMP-7 on persistent upper and lower limb non-unions.

The purpose of this study was to evaluate the efficacy and safety of recombinant bone morphogenetic protein 7 (rhBMP-7 or OP-1) as a bone-stimulating agent in the treatment of persistent fracture non-unions. Twenty-five consecutive patients [19 males, mean age 39.4 years (range: 18-79)] with 26 fracture non-unions were treated with rhBMP-7. There were 10 tibial non-unions, eight femoral, three humeral, three ulnar, one patellar, and one clavicular non-union. The mean follow-up was 15.3 months. The mean number of operations performed prior to rhBMP-7 application was 3.2, with autologous bone graft and bone marrow injection being used in 10 cases (38.5%). Both clinical and radiological union occurred in 24 (92.3%) cases, within a mean time of 4.2 months and 5.6 months, respectively. Of the remaining two cases, one patient ultimately underwent a below knee amputation, secondary to recurrence of deep sepsis. The other patient with recalcitrant ulnar non-union although the radiological union was incomplete, declined further intervention, as he was asymptomatic. No complications or adverse effects from the use of rhBMP-7 were encountered. This study supports the view that the application of rhBMP-7 as a bone-stimulating agent is safe and a power adjunct to be considered in the surgeon's armamentarium for the treatment of these challenging clinical conditions.

Biological activity of bone morphogenetic proteins (BMP's).

Bone morphogenetic proteins are multifunctional molecules having effects in many tissue types. They are members of the transforming growth factor-beta superfamily. At least 40 different types have been described to date. Their potential use in tissue regeneration has led to extensive research leading to a plethora of articles being published. This article provides a brief overview of the biological activity of different BMP's involved in the fracture healing process.

Fractures of the distal humerus in the elderly: is internal fixation the treatment of choice?

The incidence of osteoporotic fractures of the distal humerus is increasing, and the treatment of these injuries merits closer review. We assessed the results of 28 elderly patients (29 fractures) with a mean age of 85 years (range, 75-100 years). Open reduction and internal fixation was done on 21 elbows, and eight elbows were treated nonoperatively. Orthopaedic Trauma Association grading showed that the group treated with internal fixation had favorable results (three excellent, nine good, seven fair, and two poor) compared with the nonoperatively treated group (zero excellent, two good, three fair, and three poor). Mean loss of extension and mean flexion were better in the surgically treated patients (23.5 degrees and 99 degrees ) than in the nonoperatively treated patients (33.5 degrees and 71 degrees ). Substantial pain relief (mild or no pain) was achieved in a higher proportion (52%) in the surgically treated group than in the nonoperatively treated group (25%). Anatomic restoration of distal humeral tilt and articular congruity also were better in the surgically treated patients. Rates of complications were observed to be comparable to those described in the literature for younger patients. These findings reflect the relevance of surgical fixation of such fractures in this age group highlighting the need for additional clinical studies.

Radiation exposure to the hands of orthopaedic surgeons: are we underestimating the risk?

INTRODUCTION: Previous studies reported that the radiation exposure to the hands of orthopaedic surgeons was far below the acceptable limit. However, the risk could have been underestimated as some factors were overlooked, namely monitoring trainees during average workload, placing dosimeters over the most susceptible locations, measuring the cumulative dosage of radiation and considering the dose limit for non-classified workers. MATERIALS AND METHODS: We performed a prospective study in two centres to estimate the radiation dose to the hands of two consultant trauma surgeons and two trainees (one assisting and one operating) while performing 47 fluoroscopy-assisted procedures. We used validated thermoluminescent dosimeters (TLDs) rings and fingerstalls for monitoring the cumulative dosage. RESULTS: Trainees were at higher risk while performing intramedullary nailing and during assistance. Higher radiation doses were recorded from dominant index fingers and particularly fingertips. CONCLUSION: The risk of radiation exposure appears to be higher than previously reported. Fingertips are more susceptible to radiation exposure and should therefore be monitored in forthcoming studies.

p97 and close encounters of every kind: a brief review.

The AAA (ATPase associated with various cellular activities) ATPase, p97, is a hexameric protein of chaperone-like function, which has been reported to interact with a number of proteins of seemingly unrelated functions. For the first time, we report a classification of these proteins and aim to elucidate any common structural or functional features they may share. The interactors are grouped into those containing ubiquitin regulatory X domains, which presumably bind to p97 in the same way as the p47 adaptor, and into non-ubiquitin regulatory X domain proteins of different functional subgroups that may employ a different mode of interaction (assuming they also bind directly to p97 and are not experimental artifacts). Future studies will show whether interacting proteins direct p97 to different cellular pathways or a common one and structural elucidation of these interactions will be crucial in understanding these underlying functions.

The functional outcome of severe, open tibial fractures managed with early fixation and flap coverage.

We studied the outcome and functional status of 33 patients with 34 severe open tibial fractures (Gustilo grade IIIb and IIIc). The treatment regime consisted of radical debridement, immediate bony stabilisation and early soft-tissue cover using a muscle flap (free or rotational). The review included standardised assessments of health-related quality of life (SF-36 and Euroqol) and measurement of the following parameters: gait, the use of walking aids, limb-length discrepancy, knee and ankle joint function, muscle wasting and the cosmetic appearance of the limb. Personal comments and overall patient satisfaction were also recorded. The mean follow-up was 46 months (15 to 80). There were 30 Gustilo grade IIIb fractures and and four grade IIIc fractures. Of the 33 patients, 29 had primary internal fixation and four, external fixation; 11 (34%) later required further surgery to achieve union and two needed bone transport procedures to reconstruct large segmental defects. The mean time to union was 41 weeks (12 to 104). Two patients (6.1%) developed deep infection; both resolved with treatment. The mean SF-36 physical and mental scores were 49 and 62 respectively. The mean state of health score for the Euroqol was 68. Patients with isolated tibial fractures had a better outcome than those with other associated injuries on both scoring systems. Knee stiffness was noted in seven patients (21%) and ankle stiffness in 19 (56%); 12 patients (41%) returned to work. Our results compare favourably with previous outcome measurements published for both limb salvage and amputation. All patients were pleased to have retained their limbs.

Incidence and causes of mortality following acute orthopaedic and trauma admissions.

PURPOSE: To analyse the incidence and causes of mortality of orthopaedic and trauma patients. METHODS: Between March 1995 and October 2000, there were 594 (404 females) in-patient deaths (2.8%) with a mean age of 82.14 years (range, 21-102 years) out of 21,122 acute admissions. The cause of death and details of the acute episode were collected from the hospital records, death certificates and postmortem examinations. Data collected were computerised and analysed using the Astute statistical package, University of Leeds. RESULTS: The most common primary diagnosis on admission was fracture neck of femur 392 (69.1%; P = 0.001). In total, 443 (78.1%) patients underwent surgical intervention of their injuries prior to mortality with 21 patients (4.7%) dying on the same day of the operation. The mean number of days between the initial surgical intervention and death was 22.3 days (range, 0-154 days). Of the patients who were treated non-operatively, 124 died due to poor medical condition (4 [3.2%] died within 24 h, 66 [51.6%] died within the first week and the rest died thereafter). In the death certificate, the most common primary cause of death recorded in the group of patients of 64 years of age and below was cancer followed by multi-organ failure. In the age group of 65 years and above, the most common primary cause of mortality was pneumonia followed by heart failure and myocardial infarction. CONCLUSIONS: In orthopaedic and trauma patients below the age of 65 years, the most common cause of death appears to be cancer followed by multiple system organ failure; in the elderly, pneumonia predominates followed by heart failure and myocardial infarction. Proximal femoral fractures accounted for 70% of the deaths.

Distal femoral fractures: long-term outcome following stabilisation with the LISS.

We studied 29 patients with distal femoral fractures stabilised using the less invasive stabilisation system (LISS). Four patients were excluded from the final follow-up (three deaths and one case of quadriplegia). The mean age of the remaining 25 patients (9 males and 16 females) was 60.9 years and the mean follow-up 18 months (range 12-24 months). Eleven patients were tertiary referrals from other hospitals (seven cases were referred due to failure of primary fixation). Overall, there were 12 cases of high-energy trauma (7 open fractures). According to the AO classification, there were 5 Type 33A, 2 Type 33B and 12 Type 33C fractures and 4 Type 32A, 1 Type 32B, 1 Type 32C fractures. Functional assessment was performed using the modified Hospital for Special Surgery (HSS) and the Schatzker and Lambert scores. The average time to union in 22 cases was 3.5 months (range 2-5 months). All of the acute cases united without the need for bone grafting. There were three out of seven cases of non-union in the salvage group still undergoing treatment. The overall result in the acute cases was good and in the salvage cases fair. While this is a small series of patients, our preliminary data indicate favourable results using the LISS in stabilising acute distal femoral fractures. However, when the LISS is used as a revision tool the results seem to be less satisfactory. The system appears to be user-friendly and no technical difficulties were encountered.

Segmental tibial fractures: an assessment of procedures in 27 cases.

Twenty-seven patients (two women) with segmental tibial fractures (19 open) were treated in our institution with a mean age of 38.9 years (range 22-67 years) and a mean Injury Severity Score of 11.5 (9-34). Sixteen fractures were stabilised initially with an interlocking nail, seven with an external fixator, one with a hybrid external fixator, two cases were plated and one was treated in plaster. The mean size of the segment was 11.5 cm (range 4-20 cm). Soft tissue coverage was required in 17 cases. There were three cases of compartment syndrome, six cases of superficial infection and four deep infection cases (two of which required amputation). In four cases, excision of the non-viable segment was necessary. Overall, 13 patients were subjected to a second operative procedure (OP) (four external fixators were replaced with the AO solid tibial nail, two Ilizarov bone transports following excision of the dead bone segment, 2 below knee amputations, 3 exchange reamed nailings, 1 LISS plate application for stability and 1 ring fixator for compression of a fracture). Five patients underwent third procedure (two Ilizarov for bone transport, two exchange nailing, and one bone grafting). The mean time to union of the proximal segment was 38.8 weeks (range 10-78 weeks) and 41.4 weeks (range 12-65 weeks) for the distal segment, respectively. The treatment of segmental tibial fractures poses many problems to the surgeon due to the precarious blood supply of the intermediate segment. The risk of non-union delayed union, infection and additional procedures is high as seen in this series of patients.

Early internal fixation and soft tissue cover of severe open tibial pilon fractures.

We studied 32 consecutive patients with open distal tibial pilon fractures. All patients had radical debridement with immediate skeletal stabilisation and early soft-tissue cover with a vascularized muscle flap. The minimum follow-up was 1 (range 1-8) year. There were four superficial infections, two deep infections and two amputations. There were no long-term problems with union and no patient required an ankle fusion. Patients were assessed using the SF-36 questionnaire. There were significant differences from the US norm in physical function score ( p<0.01), role physical score ( p<0.05) and physical component score ( p<0.01). Physical component score of 38.5 was significantly better ( p<0.01) when compared with amputees from severe lower-extremity trauma. Our protocol for management resulted in a good functional outcome with low infection and amputation rates.

A phase II study of ZD0473 given as a short infusion every 3 weeks to patients with advanced or metastatic breast cancer: a National Cancer Institute of Canada Clinical Trials Group trial, IND 129.

BACKGROUND: ZD0473 is a new generation platinum compound with activity against a wide range of human tumor cell lines and xenografts, including carboplatin- and cisplatin-resistant lines. A phase II study of ZD0473 in advanced breast cancer was initiated by the National Cancer Institute of Canada Clinical Trials Group. PATIENTS AND METHODS: Women with metastatic breast cancer, measurable disease, an Eastern Cooperative Oncology Group performance status of up to two, and a maximum of one prior cytotoxic agent for recurrent disease were enrolled and treated at 120 mg/m(2) every 3 weeks. After 13 patients were enrolled, the dose was increased to 150 mg/m(2) on the basis of emergent data from studies ongoing at the time. RESULTS: Thirty-three women were evaluable for toxicity and 26 patients for response. Toxicity was mainly hematological with grade 3/4 thrombocytopenia in 12 of 20 patients (60%) treated at 150 mg/m(2) and grade 3 thrombocytopenia in three of 13 patients (23%) at 120 mg/m(2). Grade 3/4 neutropenia occurred in 15 patients (75%) at 150 mg/m(2) and two patients (10%) at 120 mg/m(2). Non-hematological toxicities were generally mild or moderate. There was one partial response seen for a response rate of 3.8% (95% confidence interval 0.1% to 19.5%) and stable disease in 15 patients. CONCLUSION: ZD0473 has minor activity as a single agent in metastatic breast cancer. Combinations with other drugs including docetaxel are ongoing and may be of interest.

Dorsal hamatometacarpal fracture-dislocation in a gymnast.

A rare case of unstable hamatometacarpal joint fracture-dislocation in a gymnast is presented. It was treated conservatively with successful outcome.

Injury patterns associated with mortality following motorcycle crashes.

All patients involved in motorcycle crashes admitted to various hospitals in the Yorkshire region of UK between January 1993 and December 1999 were retrospectively reviewed to identify the factors that are likely to predict a reduced survival. Of the 1239 patients requiring hospital admission, 74 died. The probability of reduced survival was estimated by a logistic regression model using independent variables such as head injury, thoracic trauma, abdominal injury, spinal injury and pelvic fracture and a compound variable of pelvic fracture combined with a long bone fracture. The odds ratio for head injury was 0.349, chest injury 0.39, abdominal injury 0.42, and the compound variable (pelvis plus a long bone fracture) 0.576. The mean injury severity score (ISS) in the fatal group was 35.96 compared to 12.2 in the group that survived (P<0.01). There was a significant difference in the Glasgow coma scale (GCS) between patients wearing a helmet and those that did not wear any protective headgear (P=0.0007). Head injury followed by chest and abdominal trauma were found to predict a reduced survival rate. Use of helmets should continue to be compulsory. Chest and abdominal injuries should be diagnosed and treated early to reduce mortality.

Friction burns within the tibia during reaming. Are they affected by the use of a tourniquet?

We have carried out a prospective, randomised trial to measure the rise of temperature during reaming of the tibia before intramedullary nailing. We studied 34 patients with a mean age of 35.1 years (18 to 63) and mean injury severity score of 10 (9 to 13). The patients were randomised into two groups: group 1 included 18 patients whose procedure was undertaken without a tourniquet and group 2, 16 patients in whom a tourniquet was used. The temperature in the bone was measured directly by two thermocouples inserted into the cortical bone near the isthmus of the tibial diaphysis. Reaming was carried out to at least 1.5 mm above the required diameter of the nail. Blood loss was assessed by recording the preoperative and postoperative haemoglobin (Hb) level. The minimum clinical follow-up was six months. In group 1 (no tourniquet), the mean Hb dropped 2.8 g/dl from 14.3 +/- 1.02 g/dl to 11.5 +/- 1.04 g/dl (p = 0.0001), whereas with the tourniquet, the mean decrease was 1.3 g/dl from 14 +/- 1 g/dl to 12.7 +/- 1.3 g/dl (p = 0.007). This difference was not statistically significant. The mean initial tibial temperature was 35.6 degrees C (SD 0.6) and rose with reaming to levels between 36.3 degrees C and 51.6 degrees C. The highest temperatures were obtained with the largest reamers (11 and 12 mm, p = 0.0001) and the most rapid rise with the smallest diameters of medullary canal (8 or 9 mm). The rise of temperature was transient (20 s). We were unable to identify any effect of the use of a tourniquet on the temperature achieved. Reamed intramedullary tibial nailing induces a transient elevation of temperature which is directly related to the amount of reaming.

The development of a new site-specific measure of quality of life for breast problems: the Cardiff breast scales.

The management of women presenting to primary care with symptoms of breast disease is of increasing interest given recent organisational changes aimed at improving accuracy and speed of referrals. As part of a randomised controlled trial, 1063 women were recruited following a primary care consultation for a variety of breast-related problems. In the absence of a suitable outcome measure for such women, a site-specific instrument was developed to complement a generic quality of life scale (SF-36). Items were generated using key informant interviews with health professionals. Draft scale items were piloted using a postal questionnaire and subsequent patient debrief interviews. A sample of respondents were also sent the same questionnaire I month later to assess test-retest reliability. Across the whole sample (n = 848), three factors were identified: 'general well-being', 'concerns' and 'relationships'. These factors accounted for 60% of total variance. Evidence of scale validity, reliability and responsiveness are reported for this new outcome measure for use in women presenting with breast problems.