Dashboard (in the) knee.

We present the case of a 19-year-old individual presenting to an orthopaedic outpatient clinic several months following a dashboard knee injury during a road traffic accident with intermittent mechanical symptoms. Despite unremarkable examination findings and normal magnetic resonance imaging, the patient was identified subsequently as having an intra-articular plastic foreign body consistent with a piece of dashboard on arthroscopic knee assessment, the retrieval of which resulted in a complete resolution of symptoms.

The local infiltration of analgesia following total knee replacement: a review of current literature.

Controversy remains regarding the optimal post-operative analgesic regimen following total knee replacement. A delicate balance is required between the provision of adequate pain relief and early mobilisation. By reviewing 29 randomised trials we sought to establish whether local infiltration of analgesia directly into the knee during surgery provides better pain relief and a more rapid rehabilitation. Although we were able to conclude that local infiltration can provide improved post-operative pain relief, and to suggest the most promising technique of administration, there is no evidence that it reduces hospital stay.

The relationship of pre- and postoperative median and ulnar nerve conduction measures to a self-administered questionnaire in carpal tunnel syndrome.

STUDY AIMS: Following carpal tunnel release (CTR), only very modest correlations have been found between subjective symptoms and function indexes compared to neurophysiological measures. The objective of this study was to evaluate this relationship by comparing the self-administered Boston symptom severity score and function severity score questionnaire against nerve conduction studies (NCS) before and after CTR using two different electrophysiological techniques. PATIENTS AND METHODS: Carpal tunnel release was performed in 51 patients (62 hands). Pre- and postoperative NCS were evaluated using both conventional neurophysiological methods and by means of a new hand-held device. RESULTS: Preoperatively there was almost no correlation between symptom severity and function scores and NCS results. Following surgery however, both symptom severity and function showed a modest, but significant improvement in their correlation to NCS (at highest r=0.405, P<0.01). This improvement in the relation of subjective measures to neurophysiological results was seen in both median nerve sensory and motor conduction as well as in ulnar nerve motor conduction. CONCLUSIONS: In addition to median-nerve dysfunction, it might be suggested that ulnar nerve changes can contribute to symptoms of carpal tunnel syndrome in patients. Several associations were found using a median-ulnar sensory latency difference in the finger-wrist segment and a sensory conduction difference in the palm to wrist segment. Significant correlations were established by both conventional NCS and the new hand-held device.

Src inhibitors in early breast cancer: a methodology, feasibility and variability study.

Early clinical trials of anticancer agents may be enriched by robust biomarkers of activity. Surrogate measures used in trials of cytotoxic agents, such as tumor size regression, may not be informative when investigating targeted agents that act principally to inhibit invasion or proliferation. This study aimed to determine the validity of invasion-related biomarkers of activity for AZD0530, a potent Src inhibitor currently in clinical development. Focal adhesion kinase (FAK) and paxillin are downstream phosphorylation substrates of Src and mediate tumor cell adhesion and invasiveness. These were therefore selected as biologically relevant markers of Src inhibition. Early breast cancer was chosen as a model as multiple samples can be collected during standard treatment and there is an intervening period in which experimental intervention can be applied. Tumor tissue was collected from diagnostic core biopsies and subsequent surgical tumor excision samples in 29 women with early breast cancer attending a single center. Protein levels were assessed quantitatively by Luminex and qualitatively by immunohistochemistry. AZD0530 inhibited tumor growth in a manner independent of dose and inhibited phosphorylation of FAK and paxillin in a dose-dependent manner in a Calu-6 xenograft model. In the clinical study, agreement of within-visit and also of between-visit measurements was high and the estimated number of patients required to detect a drug effect would be low enough to allow use of these markers as endpoints in future dose selection studies.

Dual targeting of Src and ER prevents acquired antihormone resistance in breast cancer cells.

Acquired resistance to endocrine therapies presents a major obstacle to the successful treatment of breast cancer patients. Previously, we have shown that acquisition of resistance to tamoxifen in breast cancer cells is accompanied by an elevation in Src kinase activity which promotes an aggressive, invasive phenotype in vitro. Here, we have explored the potential therapeutic effects of combining Src inhibition with anti-oestrogen treatment on the development of endocrine insensitivity in breast cancer cells. Treatment of MCF7 and T47D cells with tamoxifen alone resulted in an initial growth inhibitory phase followed by the eventual development of tamoxifen resistance together with an elevation of Src kinase activity, which was central to their increased invasive capacity. Chronic exposure of both cell types to the Src inhibitor, AZD0530, as a monotherapy resulted in outgrowth of AZD0530-resistant cells, in which Src kinase activity remained suppressed as did their in vitro invasive nature. Treatment of both MCF7 and T47D cells with AZD0530 in combination with tamoxifen resulted in a reduction of Src activity together with inhibition of focal adhesion kinase phosphorylation and a complete abrogation of their in vitro invasive behaviour. Furthermore, combination therapy significantly suppressed expression of cyclinD1 and c-myc and prevented cell proliferation and the subsequent emergence of a resistant phenotype, with total cell loss occurring by 12 weeks. These data demonstrate that pharmacological targeting of Src kinase, in conjunction with antihormone therapies, effectively prevents antihormone resistance in breast cancer cells in vitro and suggests a potential novel therapeutic benefit of Src kinase inhibitors clinically.

An uncommon cause of back pain in pregnancy.

Back pain is a major cause of disability worldwide. A case of a 29 year old Caucasian woman with low back pain secondary to an uncommon benign condition called osteitis condensans ilii is presented and the literature is reviewed. Limited information in the literature combined with poor awareness across the specialty and among the primary care physicians leads to an extensive investigation and misdiagnosis of this benign condition. This report emphasis the salient features and the differential diagnosis in diagnosing and managing this rare condition.

Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children.

BACKGROUND: A randomized, prospective, double-blind study of 29 children was performed to evaluate the hypothesis that dexamethasone administration prior to cardiopulmonary bypass would decrease the inflammatory mediator release and improve the postoperative clinical course. METHODS: Fifteen children received dexamethasone (1 mg/kg intravenously) and 14 (controls) received saline solution 1 hour prior to CPB. Serial blood analyses for interleukin-6, tumor necrosis factor-alpha, complement component C3a, and absolute neutrophil count were performed. Postoperative variables evaluated included temperature, supplemental fluids, alveolar-arterial oxygen gradient, and days of mechanical ventilation. RESULTS: Dexamethasone caused an eightfold decrease in interleukin-6 levels and a greater than threefold decrease in tumor necrosis factor-alpha levels after CPB (p < 0.05). Complement component C3a and absolute neutrophil count were not affected by dexamethasone. The mean rectal temperature for the first 24 hours postoperatively was significantly lower in the group given dexamethasone than in the controls (37.2 degrees +/- 0.4 degrees C versus 37.7 degrees +/- 4 degrees C; p = 0.007). Dexamethasone-treated patients required less supplemental fluid during the first 48 hours (22 +/- 28 mL/kg versus 47 +/- 34 mL/kg; p = 0.04). Compared with controls, dexamethasone-treated children had significantly lower alveolar-arterial oxygen gradients during the first 24 hours (144 +/- 108 mm Hg versus 214 +/- 118 mm Hg; p = 0.02) and required less mechanical ventilation (median duration, 3 days versus 5 days; p = 0.02). CONCLUSIONS: Dexamethasone administration prior to CPB in children leads to a reduction in the postbypass inflammatory response as assessed by cytokine levels and clinical course.

Randomised, prospective study comparing cemented and cementless total knee replacement: results of press-fit condylar total knee replacement at five years.

Early implants for total knee replacement were fixed to bone with cement. No firm scientific reason has been given for the introduction of cementless knee replacement and the long-term survivorship of such implants has not shown any advantage over cemented forms. In a randomised, prospective study we have compared cemented and uncemented total knee replacement and report the results of 139 prostheses at five years. Outcome was assessed both clinically by independent examination using the Nottingham knee score and radiologically using the Knee Society scoring system. Independent statistical analysis of the data showed no significant difference between cemented and cementless fixation for pain, mobility or movement. There was no difference in the radiological alignment at five years, but there was a notable disparity in the radiolucent line score. With cemented fixation there was a significantly greater number of radiolucent lines on anteroposterior radiographs of the tibia and lateral radiographs of the femur. At five years, our clinical results would not support the use of the more expensive cementless fixation whereas the radiological results are of unknown significance. Longer follow-up will determine any changes in the results and conclusions.

The role of the centrifugal pump in hemolysis during neonatal extracorporeal support.

While the use of the centrifugal vortex ECMO pump as an alternative to a roller-occlusion pump offers distinct advantages, unacceptable hemolysis may occur during its use in newborn infants. The authors studied 87 consecutive neonatal patients with respiratory failure supported with venoarterial ECMO using a centrifugal vortex pump. Baseline mean plasma free hemoglobin level for all patients during the first 48 hours of bypass was 31.3 +/- 3.1 md/dl. In 51 patients, an abrupt rise in the plasma free hemoglobin occurred. In 48 of 51 patients, the pump head alone was changed at 91.9 +/- 6.6 hours after initiation of bypass. Mean plasma free hemoglobin decreased to baseline values following pump head change. The authors could not determine any factors that distinguish the infants who developed hemolysis from those who did not. Changing only the pump head provides a simple approach to hemolysis during use of the centrifugal vortex pump on newborn infants.

The impact of extracorporeal membrane oxygenation on survival in pediatric patients with acute respiratory failure. Pediatric Critical Care Study Group.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency in the treatment of acute respiratory failure in pediatric patients. Our objective in this study was to test the hypothesis that ECMO improves outcome in pediatric patients with acute respiratory failure. DESIGN: Multicenter, retrospective cohort analysis. SETTING: Forty one pediatric intensive care units participated in the study under the auspices of the Pediatric Critical Care Study Group. PATIENTS: All pediatric patients admitted to the participating institutions with acute respiratory failure during 1991 were included. Patients with congenital heart disease, contraindications to ECMO, or incomplete data were excluded, yielding a data set of 331 patients from 32 hospitals. INTERVENTIONS: Conventional mechanical ventilation, high-frequency ventilation, and extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Multivariate logistic regression analysis was used to identify factors associated with survival. In a second analysis, pairs of ECMO and non-ECMO patients, matched by severity of disease and respiratory diagnosis, were compared. The use of ECMO (p = .0082), but not the use of high-frequency ventilation, was associated with a reduction in mortality. Other factors independently associated with mortality included oxygenation index (p < .0001), Pediatric Risk of Mortality score (PRISM) (p < .0001) and the Paco2 (p = .045). In 53 diagnosis- and risk-matched pairs, there was a significantly lower mortality rate (26.4% vs. 47.2%; p < .01) in the ECMO-treated patients. When all patients were stratified into mortality risk quartiles on the basis of oxygenation index and PRISM score, the proportion of deaths among ECMO-treated patients in the 50% to 75% mortality risk quartile was less than half the proportion in the non-ECMO treated patients (28.6% vs. 71.4% p < .05)> No effect was seen in the other quartiles. CONCLUSIONS: The use of ECMO was associated with an improved survival in pediatric patients with respiratory failure. The lack of association of outcome with treatment in the ECMO-capable hospital or with another tertiary technology (i.e. high-frequency ventilation) suggests that ECMO itself was responsible for the improved outcome. Further studies of this procedure are warranted but require broad-based multi-institutional participation to provide sufficient statistical power and sensitivity to demonstrate efficacy.

Sustained loading generates stress concentrations in lumbar intervertebral discs.

STUDY DESIGN: Cadaveric motion segment experiment. Measurements on each specimen were compared before and after creep loading. OBJECTIVES: To show how sustained "creep" loading affects stress distributions inside intervertebral discs. SUMMARY OF BACKGROUND DATA: The central region of an intervertebral disc acts like a hydrostatic "cushion" between adjacent vertebrae. However, this property depends on the water content of the tissues and may be lost or diminished after creep. METHODS: Twenty-seven lumbar motion segments consisting of two vertebrae and the intervening disc and ligaments were loaded to simulate erect standing postures in life. The distribution of compressive stress in the disc matrix was measured by pulling a miniature pressure transducer through the disc in the midsagittal plane. Profiles of vertical and horizontal compressive stress were repeated after each specimen had been creep loaded in compression for 2-6 hours. RESULTS: Creep reduced the hydrostatic pressure in the nucleus by 13-36%. Compressive stresses in the anulus were little affected when the profiles were measured at 1 kN, but at 2 kN, localized peaks of compressive stress appeared (or grew in size) in the posterior anulus after creep. CONCLUSIONS: Increased loading of the apophysial joints causes an overall reduction in intradiscal stresses after creep. In addition, water loss from the nucleus causes a transfer of load from nucleus to anulus. Stress concentrations may lead to pain, structural disruption, and alterations in chondrocyte metabolism. Disc mechanics depend on loading history as well as applied load.

Probability of survival after prolonged extracorporeal membrane oxygenation in pediatric patients with acute respiratory failure. Extracorporeal Life Support Organization.

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) has been used with increasing frequency for respiratory failure that is unresponsive to conventional therapy. We examined the relationship between duration of ECMO and outcome to understand whether prolonged ECMO (duration of the procedure for > 14 days) was more commonly associated with futile therapy or eventual recovery. DESIGN: A cohort study of all patients reported to the Pediatric ECMO Registry for Acute Respiratory Failure of the Extracorporeal Life Support Organization. SETTING: Tertiary hospitals (n = 83) capable of providing extracorporeal support for pediatric patients. PATIENTS: Children (n = 382) between the ages of 1 wk and 18 yrs of age with severe respiratory failure. INTERVENTIONS: Extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: The death or live hospital discharge of ECMO-treated patients, together with the post-ECMO mechanical ventilation course, were examined as a function of duration of ECMO and of pre-ECMO respiratory status. The occurrence of complications and the causes of death were also noted. The criteria used to initiate ECMO, as well as the determination of the futility of further ECMO, were determined by local practice at individual centers. There were 382 patients treated with ECMO, of whom 184 (48%) survived. The proportional survival in the patients treated for the longest duration was similar to the overall group. The cause of death was given for 168 patients: 32 neurologic deaths; nine deaths due to ECMO complications; and 30 deaths due to nonpulmonary organ failure. There were 97 deaths due to elective ECMO termination; 80 of these deaths occurred after the determination of the futility of anticipating pulmonary recovery. The latter deaths occurred at widely varying durations of ECMO, with a median of 282 hrs. However, at that same duration, 47 eventual survivors (26% of all survivors) continued to receive ECMO. By discriminant analysis, the survival rate was independently related (r2 = .18; p < .0001) to peak ventilator inspiratory pressure before ECMO and duration of intubation before ECMO, patient age, and the occurrence of several complications. CONCLUSIONS: While the survival rate in pediatric patients receiving ECMO appears related to the severity of lung disease and to the occurrence of ECMO complications, the survival rate in patients treated with ECMO courses of > 2 wks was similar to the survival rate of patients treated for shorter periods of time. ECMO was terminated in some patients for pulmonary futility at durations of ECMO associated with survival in substantial numbers of patients in whom ECMO was continued.

Spondylolysis. Bending of the inferior articular processes of lumbar vertebrae during simulated spinal movements.

STUDY DESIGN: This was a cadaveric lumbar motion segment experiment. OBJECTIVES: To measure bending about the pars interarticularis during simulated flexion and extension movements, with and without high compressive forces. This was designed to indicate which activities are most likely to cause spondylolysis. SUMMARY OF BACKGROUND DATA: The mechanical etiology of spondylolysis is controversial. METHODS: Motion segments were loaded to simulate: A, full flexion; B, full extension; C, high compression in flexed posture, and D, high compression in lordotic posture. Bending of the inferior articular processes about the pars was measured in the sagittal plane, using a two-dimensional "MacReflex" infrared motion analysis system. RESULTS: In full flexion, tension in the intervertebral ligaments bent the processes forward and down (by 3.25 degrees +/- 3.07 degrees), whereas in the loading conditions B, C, and D, inter-facet compressive forces caused the processes to bend backward and upward, by 2.24 +/- 2.48 degrees, 0.40 +/- 0.23 degrees, and 0.74 +/- 0.56 degrees respectively. CONCLUSIONS: Activities that involve alternating flexion and extension movements cause large stress reversals in the pars and pose the greatest threat of spondylolysis. Compressive loading has little effect.