Investigation of thermally induced damage to surrounding nerve tissue when using curettage and cementation of long bone tumours, modelled in cadaveric porcine femurs.

INTRODUCTION: Curettage with cement augmentation is a technique used in the treatment of bone tumours. Thermal energy released during the cement polymerisation process can damage surrounding tissues. This study aims to record temperature changes at various sites on and around bone during the cementing process. We hypothesised that adjacent structures, such as the radial nerve, may be threatened by this process in the clinical setting. MATERIALS AND METHODS: Using 18 porcine femurs as a model of the human humerus, we used thermocouples and a thermal imaging camera to measure changes in temperature during the cementing process. Fractures were created in nine samples to establish whether a discontinuity of the cortex had an effect on thermal conduction. RESULTS: Significantly higher temperatures were recorded in samples with a fracture compared to those without a fracture. The site overlying the centre of the cement bolus (hypothetical site of the radial nerve) demonstrated higher temperatures than all other sites on the same cortex. When considering the radial nerve site, over half the samples demonstrated temperatures exceeding 47 °C for over a minute. When a threshold of 50 °C for more than 30 s was considered, three samples without a fracture exceeded this value compared to two with a fracture. CONCLUSION: The temperatures recorded were sufficient to cause damage to neural tissue. Limiting thermal exposure to soft tissues is recommended. Increased attention is required when using larger cement boluses, or where bone quality is poor or a fracture, iatrogenic or preexisting, is present.

A combined light sheet fluorescence and differential interference contrast microscope for live imaging of multicellular specimens.

We describe a microscope capable of both light sheet fluorescence microscopy and differential interference contrast microscopy (DICM). The two imaging modes, which to the best of our knowledge have not previously been combined, are complementary: light sheet fluorescence microscopy provides three-dimensional imaging of fluorescently labelled components of multicellular systems with high speed, large fields of view, and low phototoxicity, whereas differential interference contrast microscopy reveals the unlabelled neighbourhood of tissues, organs, and other structures with high contrast and inherent optical sectioning. Use of a single Nomarski prism for differential interference contrast microscopy and a shared detection path for both imaging modes enables simple integration of the two techniques in one custom microscope. We provide several examples of the utility of the resulting instrument, focusing especially on the digestive tract of the larval zebrafish, revealing in this complex and heterogeneous environment anatomical features, the behaviour of commensal microbes, immune cell motions, and more.

Preoperative assessment and optimisation for pelvic exenteration in locally advanced and recurrent rectal cancer: A review.

The pre-operative phase in planning a pelvic exenteration or extended resections is critical to optimising patient outcomes. This review summarises the key components of preoperative assessment and planning in patients with locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LLRC) being considered for potential curative resection. The preoperative period can be considered in 5 key phases: 1) Multidisciplinary meeting (MDT) review and recommendation for neoadjuvant therapy and surgery, 2) Anaesthetic preoperative assessment of fitness for surgery and quantification of risk, 3) Shared decision making with the patient and the process of informed consent, 4) Prehabilitation and physiological optimisation 5) Technical aspects of surgical planning. This review will focus on patients who have been recommended for surgery by the MDT and have completed neoadjuvant therapy. Other important considerations beyond the scope of this review are the various neoadjuvant strategies employed which in this patient group include Total Neo-adjuvant Therapy and reirradiation. Critical to improving perioperative outcomes is the dual aim of achieving a negative resection margin in a patient fit enough for extended surgery. Advanced, realistic communication is required pre-operatively and should be maintained throughout recovery. Optimising patient's physiological and psychological reserve with a preoperative prehabilitation programme is important, with physiotherapy, psychological and nutritional input. From a surgical perspective, image based technical preoperative planning is important to identify risk points and ensure correct surgical strategy. Careful attention to the entire patient journey through these 5 preoperative phases can optimise outcomes with the accumulation of marginal gains at multiple timepoints.

Morbidity and mortality after closure of loop ileostomy.

BACKGROUND: A temporary loop ileostomy is commonly used to protect low pelvic anastomoses. Closure is associated with morbidity and mortality. This study investigated patterns of complications after loop ileostomy closure and factors associated with morbidity and mortality. METHOD: A review was performed of patients who underwent loop ileostomy closure between 1999 and 2005. RESULTS: Three hundred and twenty-five patients underwent closure of loop ileostomy. Reasons for primary surgery were: anterior resection for cancer (n = 160, 49%), ileal pouch-anal anastomosis (n = 114, 35%), diverticular disease (n = 25, 8%), Crohn's colitis (n = 4, 1%) and other conditions (n = 22, 7%). Overall mortality was 2.5% (n = 8) and morbidity was 22.8% (n = 74). Thirty-two patients (10%) developed small bowel obstruction, of whom seven required operative intervention. Overall, the re-operation rate in this series was 28 patients (8.6%). Thirteen (4%) patients had an anastomotic leak of whom 12 patients had re-operation. Preoperative anaemia was significantly associated with leakage (Hb < 11 g/dl; n = 65, P = 0.033). The leakage rate was lower after a stapled anastomosis than a hand-sutured anastomosis (4/203 vs 9/122; P = 0.039). Hypo-albuminaemia (albumin < 34 g/l) was significantly associated with mortality (n = 46, P < 0.001). CONCLUSIONS: Loop ileostomy closure is associated with morbidity and mortality. Anaemia and hypo-albuminaemia may be associated with poor outcome.

Image velocimetry and spectral analysis enable quantitative characterization of larval zebrafish gut motility.

BACKGROUND: Normal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Previous image analysis approaches have successfully extracted properties related to the temporal frequency of motility modes, but robust measures of contraction magnitude, especially from in vivo image data, remain challenging to obtain. METHODS: We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motion. KEY RESULTS: We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild types. CONCLUSIONS & INFERENCES: Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements.

An Inducible Reconstitution System for the Real-Time Kinetic Analysis of Protease Activity and Inhibition Inside the Membrane.

Intramembrane proteases are an ancient and diverse group of multispanning membrane proteins that cleave transmembrane substrates inside the membrane to effect a wide range of biological processes. As proteases, a clear understanding of their function requires kinetic dissection of their catalytic mechanism, but this is difficult to achieve for membrane proteins. Kinetic measurements in detergent systems are complicated by micelle fusion/exchange, which introduces an additional kinetic step and imposes system-specific behaviors (e.g., cooperativity). Conversely, kinetic analysis in proteoliposomes is hindered by premature substrate cleavage during coreconstitution, and lack of methods to quantify proteolysis in membranes in real time. In this chapter, we describe a method for the real-time kinetic analysis of intramembrane proteolysis in model liposomes. Our assay is inducible, because the enzyme is held inactive by low pH during reconstitution, and fluorogenic, since fluorescence emission from the substrate is quenched near lipids but restored upon proteolytic release from the membrane. The precise measurement of initial reaction velocities continuously in real time facilitates accurate steady-state kinetic analysis of intramembrane proteolysis and its inhibition inside the membrane environment. Using real data we describe a step-by-step strategy to implement this assay for essentially any intramembrane protease.

Total hip arthroplasty and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck. A randomized, controlled trial.

BACKGROUND: Hemiarthroplasty and total hip arthroplasty are commonly used to treat displaced intracapsular fractures of the femoral neck, but each has disadvantages and the optimal treatment of these fractures remains controversial. METHODS: In the present prospectively randomized study, eighty-one patients who had been mobile and lived independently before they had sustained a displaced fracture of the femoral neck were randomized to receive either a total hip arthroplasty or a hemiarthroplasty. The mean age of the patients was seventy-five years. Outcome was assessed with use of the Oxford hip score, and final radiographs were assessed. RESULTS: After a mean duration of follow-up of three years, the mean walking distance was 1.17 mi (1.9 km) for the hemiarthroplasty group and 2.23 mi (3.6 km) for the total hip arthroplasty group, and the mean Oxford hip score was 22.3 for the hemiarthroplasty group and 18.8 for the total hip arthroplasty group. Patients in the total hip arthroplasty group walked farther (p=0.039) and had a lower (better) Oxford hip score (p=0.033) than those in the hemiarthroplasty group. Twenty of thirty-two living patients in the hemiarthroplasty group had radiographic evidence of acetabular erosion at the time of the final follow-up. None of the hips in the hemiarthroplasty group dislocated, whereas three hips in the total hip arthroplasty group dislocated. In the hemiarthroplasty group, two hips were revised to total hip arthroplasty and three additional hips had acetabular erosion severe enough to indicate revision. In the total hip arthroplasty group, one hip was revised because of subsidence of the femoral component. CONCLUSIONS: Total hip arthroplasty conferred superior short-term clinical results and fewer complications when compared with hemiarthroplasty in this prospectively randomized study of mobile, independent patients who had sustained a displaced fracture of the femoral neck.

Treatment of the young active patient with osteoarthritis of the hip. A five- to seven-year comparison of hybrid total hip arthroplasty and metal-on-metal resurfacing.

We compared the five- to seven-year clinical and radiological results of the metal-on-metal Birmingham hip resurfacing with a hybrid total hip arthroplasty in two groups of 54 hips, matched for gender, age, body mass index and activity level. Function was excellent in both groups, as measured by the Oxford hip score, but the Birmingham hip resurfacings had higher University of California at Los Angeles activity scores and better EuroQol quality of life scores. The total hip arthroplasties had a revision or intention-to-revise rate of 8%, and the Birmingham hip resurfacings of 6%. Both groups demonstrated impending failure on surrogate end-points. Of the total hip arthroplasties, 12% had polyethylene wear and osteolysis under observation, and 8% of Birmingham hip resurfacings showed migration of the femoral component. Polyethylene wear was present in 48% of the hybrid hips without osteolysis. Of the femoral components in the Birmingham hip resurfacing group which had not migrated, 66% had radiological changes of unknown significance.

1.9 A resolution crystal structure of the Saccharomyces cerevisiae Ran-binding protein Mog1p.

The 1.9 A resolution X-ray crystal structure of Ran-binding protein Mog1p shows that it has a unique fold based on a six-stranded antiparallel beta-sheet backed on both sides by an extensive alpha-helix. The topology of some elements of Mog1p secondary structure resemble a portion of nuclear transport factor 2 (NTF2), but the hydrophobic cavity and surrounding negatively charged residues that are important in the NTF2-RanGDP interaction are not conserved in Mog1p. In addition to binding RanGTP, Mog1p forms a 1:1 complex with RanGDP and so binds Ran independent of its nucleotide state. Mog1p and NTF2 compete for binding to RanGDP indicating that their binding sites on RanGDP are sufficiently close to prevent both proteins binding simultaneously. Although there may be some overlap between the Mog1p and NTF2 binding sites on RanGDP, these sites are not identical. Sequence analysis of Mog1p homologues from Schizosaccharomyces pombe, human, and Caenorhabditis elegans in the context of the Mog1p crystal structure indicates the presence of a cluster of highly conserved surface residues consistent with an interaction site for Ran.

Molecular mechanism of translocation through nuclear pore complexes during nuclear protein import.

The trafficking of macromolecules between cytoplasm and nucleus through nuclear pore complexes is mediated by specific carrier molecules such as members of the importin-beta family. Nuclear pore proteins (nucleoporins) frequently contain sequence repeats based on FG cores and carriers appear to move their cargo through the pores by hopping between successive FG cores. A major question is why some macromolecules are transported while others are not. This selectivity may be generated by the ability to bind FG repeats, a local concentration of carrier-cargo complexes near the entrance to the pore channel, and steric hindrance produced by high concentrations of nucleoporins in the channel.

Vasopressin's effects on acquisition and extinction of conditioned avoidance response to smoking.

Lysine-8-vasopressin (LVP) 5 I.U. or NaCl was administered intranasally daily for 5 days in a double blind study to 14 women and 7 men volunteers, 30 minutes prior to aversive conditioning sessions designed to assist them to stop smoking. Subjects were asked to record the number of urges to smoke, the strength of their strongest urge to smoke and the number of cigarettes smoked on a daily basis. Adequate data was obtained from 17 subjects for the Lead-in (pretreatment) week and for the Treatment week. Of these, 10 continued to supply sufficient responses through the sixth week of follow-up. During the week of aversive conditioning those subjects receiving LVP smoked significantly fewer cigarettes than the saline treatment group (p less than 0.01). During the Follow-up period the LVP group had significantly more urges to smoke than the saline group (p less than 0.01). The LVP group also smoked significantly more cigarettes than the saline group 4 weeks (p less than 0.05) and 6 weeks (0.01) after the Treatment week. LVP was associated with a facilitation of the acquisition of the avoidance response to smoking followed by an apparent acceleration of the extinction of the avoidance response compared to saline.

Experience with the neodymium:yttrium-aluminum-garnet laser in forty-two cases.

The neodymium:yttrium-aluminum-garnet (Nd:YAG) laser has been utilized in the treatment of 42 cases during the past 2 years at two institutions. The laser was used under investigational permits from the Food and Drug Administration. It was found to be of particular value in the treatment of vascular intracranial tumors, especially meningiomas, and metastatic tumors of the spine. The ability of the laser to shrink and devascularize these tumors was efficacious as a surgical adjunct. Laser treatment of tumor attachments, especially those of meningiomas to the skull base, seemed to be effective in eradication of residual tumor. Long term benefits of such therapy, however, remain unproven. Because of the penetrating ability of the Nd:YAG laser beam, this device must be used with care by surgeons experienced in its use to prevent injury to adjacent structures.

Complete fracture-dislocation of cervical spine without permanent neurological sequelae. Case report.

A case of complete fracture-dislocation of the lower cervical spine in which there were no permanent neurological sequelae is presented. The absence of permanent neurological deficits with this type of injury is rare. The primary mechanism of injury in this patient was believed to be hyperextension with rupture of the ligamentous structures, allowing complete dislocation of the C-6 body while the posterior elements remained in good alignment due to multiple fractures which "decompressed" the spinal cord.

Shunt fluid examination: risks and benefits in the evaluation of shunt malfunction and infection.

A combined retrospective and prospective study was designed to assess the efficacy of shunt fluid examination in the evaluation of shunt malfunction and/or infection, and to ascertain the complication rate associated with this procedure. Ninety-one patients with shunts for the treatment of hydrocephalus underwent a total of 209 diagnostic shunt "taps." Of 72 instances of mechanical obstruction documented at surgery, 70 were correctly identified by abnormal shunt fluid dynamics, either an opening cerebrospinal fluid (CSF) pressure in excess of the expected valve pressure or absent flow of fluid. The organisms responsible for 12 of 13 shunt-related infections were correctly isolated on initial and all subsequent shunt fluid cultures obtained prior to the institution of appropriate antibiotics. With one infection, a bacterial pathogen was not identified until the third tap. In all instances in which lumbar or ventricular CSF, blood, or wound cultures disclosed an organism, shunt fluid cultures also identified the agent. In addition, these procedures were less reliable. No complications occurred during or immediately following any of the shunt taps. Long-term consequences were assessed in 53 patients with an average follow-up period of 26 months. Some shunt systems subsequently required revision and two infections were documented. The uniformly long interval between the shunt fluid examination and these complications makes it unlikely that the taps contributed to the development of malfunction or infection. Shunt fluid examination appears to be a simple, benign, and yet accurate means of diagnosing shunt malfunction and/or shunt-related infection.

Regional cerebral blood flow and metabolism in reversible ischemia due to vasospasm. Determination by positron emission tomography.

Regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of oxygen (rCMRO2) were measured by positron emission tomography (PET) in four patients with subarachnoid hemorrhage and hemiparesis due to cerebral vasospasm. With resolution of the vasospasm, two patients recovered and two remained hemiparetic. Contralateral to the hemiparesis, rCBF was slightly higher in the two patients who eventually recovered (15.0 and 16.2 ml/100 gm/min) than in the two who remained hemiparetic (12.0 and 11.7 ml/100 gm/min). The rCMRO2 measurements showed similar differences, with values of 1.34 and 2.60 ml/100 gm/min in the patients who recovered, and 0.72 and 1.66 ml/100 gm/min in those who did not. These preliminary findings indicate that with PET studies it may be possible to prospectively differentiate patients with neurological deficits due to reversible ischemia from patients with irreversible infarction.

The preschool behavioral classification project: An initial report.

The Behavioral Classification Project (BCP), previously developed for children from 6-13 years of age, was extended to the preschool ages, the goal being to establish factorial dimensions of problem and nonproblem behaviors of children from 4 to 6 years of age. Initially, behavioral items on the BCP form not applicable to preschoolers were eliminated and replaced with new items. When completed, the Preschool Behavioral Classification Project (PBCP) form contained 268 behavioral items and 5 demographic variables. Forms were administered to 1,350 parents of 4-, 5-, and 6-year-olds, and 668 usable forms were returned. Analysis of the data was done by means of the principal components method in which the data were rotated first to orthogonal simple structure and then to oblique simple structure. Twenty-two clearly delineated factors which made nosological sense were obtained. Five additional factors were extracted and although they were not clearly defined dimensions, they contained important behavioral items.

Head injury at the southeastern Georgia Regional Trauma Center: a three-year review.

The impact of head injury on our trauma center is significant because of the large number of cases with their heavy utilization of trauma center resources. Head injury also exerts a major influence on the Trauma Center in a rural area since it serves as a major provider of care for the head injured over a wide geographical area. Mortality rates seen in this population compare favorably with contemporary data from other studies using GCS and Head AIS as indicators of level of injury.

A medium-term comparison of hybrid hip replacement and Birmingham hip resurfacing in active young patients.

We compared the medium-term clinical and radiological results of hybrid total hip replacement (THR) with metal-on-metal Birmingham hip resurfacing (BHR) in two groups of 54 young patients matched for age, gender, body mass index and pre-operative levels of activity. The clinical outcome was assessed by the University of California, Los Angeles (UCLA) activity score, the Oxford Hip Score (OHS) and the EuroQol scores. Radiologically, all hips were assessed for migration and osteolysis, the hybrid THRs for polyethylene wear and the BHRs for a pedestal sign. The mean follow-up of the patients with a hybrid THR was ten years and for those with a BHR, nine years. Four patients with a hybrid THR and one with a BHR had died. In each group five were lost to follow-up. The revision rate of the hybrid THRs was 16.7% (9 of 54) and of the BHRs 9.3% (5 of 54) (p = 0.195). Radiographs of a further eight hybrid THRs demonstrated wear and osteolysis, and they await revision (p = 0.008). Of the unrevised BHRs 90% had radiological changes, of which approximately 50% had progressed over the previous four years. All hybrid THRs demonstrated linear polyethylene wear with a mean of 1.24 mm (0.06 to 3.03). The BHRs recorded superior OHS (p = 0.013), UCLA (p = 0.008), and EuroQol visual analogue scores (p = 0.009). After nine years, patients with BHRs remained more active and had a lower rate of revision than those with hybrid THRs. Both groups demonstrated progressive radiological changes at medium-term follow-up.

Total hip replacement and hemiarthroplasty in mobile, independent patients with a displaced intracapsular fracture of the femoral neck: a seven- to ten-year follow-up report of a prospective randomised controlled trial.

We reviewed the seven- to ten-year results of our previously reported prospective randomised controlled trial comparing total hip replacement and hemiarthroplasty for the treatment of displaced intracapsular fracture of the femoral neck. Of our original study group of 81 patients, 47 were still alive. After a mean follow up of nine years (7 to 10) overall mortality was 32.5% and 51.2% after total hip replacement and hemiarthroplasty, respectively (p = 0.09). At 100 months postoperatively a significantly greater proportion of hemiarthroplasty patients had died (p = 0.026). Three hips dislocated following total hip replacement and none after hemiarthroplasty. In both the total hip replacement and hemiarthroplasty groups a deterioration had occurred in walking distance (p = 0.02 and p < 0.001, respectively). One total hip replacement required revision compared with four hemiarthroplasties which were revised to total hip replacements. All surviving patients with a total hip replacement demonstrated wear of the cemented polyethylene component and all hemiarthroplasties had produced acetabular erosion. There was lower mortality (p = 0.013) and a trend towards superior function in patients with a total hip replacement in the medium term.