A prospective randomized study of ACL-reconstructions using bone-patellar tendon-bone grafts fixed with bioabsorbable or metal interference screws.

INTRODUCTION: Bioabsorbable screws are, at the expense of metal screws, increasingly used as fixation device in ACL-reconstructions. The possible advantages with bioabsorbable screws are better postoperative MRI evaluations and easier revision surgery. PURPOSE: The aim of this study was to compare the clinical outcome after ACL-reconstructions with BPTB-grafts fixed with metal interference screws or bioabsorbable screws 7 years postoperatively. The resorption of the bioabsorbable screws was also analyzed. METHODS: Between 2000 and 2001, 41 patients with ACL deficient knees were randomized for the use of BPTB-graft fixed with either metal interference screws or bioabsorbable poly-L: -lactic acid screws. This is a 7-year follow-up with clinical examinations of both groups and, MRI of the patients with bioabsorbable screws. RESULTS: The clinical and functional results were satisfactory in both groups. There were no significant differences between the groups in any parameter measured, except for better Pivot shift results in the bioscrew group (P = 0.04). The MRI evaluation showed degradation of the bioscrews. A residual screw tract which appeared threaded was seen in the tibia in 11 of the 16 patients. There was no sign of bony ingrowth in the previous screw site in the tibia in any of the patients. CONCLUSION: The potential advantages of using PLLA-screws compared to metal screws are not sufficient to warrant the routine use of PLLA-screws in ACL-reconstructions. LEVEL OF EVIDENCE: I.

Clinical and MRI findings after high dosage medical exercise therapy in patients with long lasting subacromial pain syndrome: a case series on six patients.

UNLABELLED: SUMMARY BACKGROUND AND PURPOSE: The primary aim of this case series was to investigate the effect of a high dosage medical exercise therapy program on shoulder pain in patients with subacromial pain syndrome. SUBJECTS: Six subjects were assigned to a medical exercise therapy group. METHODS: They received three treatments a week over three months. Outcome measures were descriptions of the subacromial space including supraspinatus tendon diameter, function, pain, and active range of motion in the shoulder girdle. RESULTS: The subjects showed improvement posttest compared to pretest with respect to pain, function, range of motion, and isometric strength. An MRI demonstrated no change in tendon thickness after the treatment. Inflammatory signs such as fluid in the subacromial bursa decreased in some patients. DISCUSSION AND CONCLUSION: In patients with uncomplicated subacromial pain syndrome, high dosage medical exercise therapy might be an efficient treatment approach. The clinical effects might be explained by morphological changes in the subacromial space.

Multimodal cancer treatment: real time monitoring, optimization, and synergistic effects.

The primary objective of this analysis is to provide the theoretical framework for a novel multimodal cancer treatment system emphasizing the use of ultrasound as a synergistic drug release mechanism, real time monitoring by MRI of hyperthermic, pO2, and ultrasound induced released effects. The aim is to provide a cure for the 20% of cancer victims who will die of complications from local solid tumors. Adjuvant therapy usually refers to surgery preceding or following chemotherapy and/or ionizing radiation treatment to decrease the risk of recurrence, but the absolute benefit for survival obtained with adjuvant therapy compared to control is only approximately 6%. Tumor hypoxia represents a primary therapeutic concern, besides multi-drug resistance (MDR), because it can reduce the effectiveness of drugs and radiotherapy; well-oxygenated cells require one-third the dose of hypoxic cells to achieve a given level of cell killing. The era of systemic and indiscriminate chemotherapeutic drug delivery into both healthy and pathologic tissues is near an end. Targeted drug delivery using nanoparticles is emerging as the new vehicle, either as a single treatment option, as part of adjuvant procedures or as a component of a multimodal cancer treatment system. There are more than 100 nanosized liposomes or particles, and conjugated anticancer agents in various stages of preclinical and clinical development. Active targeting can be achieved by site-specific delivery or site-specific triggering. Ultrasound can be utilized as both a site triggering and synergistic mechanism in drug release. The process can be monitored using MRI by a physical process called cavitation. An analysis of low frequency ultrasound exposure in combination with liposomally encapsulated doxorubicin (Caelyx) on Balb/c nude mice inoculated with a WiDr (human colon cancer) tumor cell line provided tumor growth inhibition of 30-40%. Mild hyperthermia causes mean intra-tumor pO2 to increase by 25% and enhances tumor radiosensitization. Hyperthermia causes the extravasation of liposome nanoparticles in deep tumor regions. Ionizing radiation improves the distribution and uptake of drugs. Liposomally encapsulated drugs and ultrasound mediated hyperthermia have been proven to circumvent MDR effects. Hyperthermic effects and pO2 monitoring of bodily fluid have been performed by MRI. It is hypothesized that increased vascularization and subsequent increase in pO2 levels to hypoxic regions, and monitoring of drug release through cavitation, can facilitate optimized real time concomitant or sequential treatments of drug therapy, hyperthermia, ionizing radiation, etc., before or after surgery. An improved therapeutic index with the use of the outlined system seems probable.

Abnormal cerebral MRI findings and neuroimpairments in very low birth weight (VLBW) adolescents.

BACKGROUND: High prevalence of abnormal cerebral MRI findings as well as major and minor motor, perceptual and cognitive impairments has been reported in very low birth weight (VLBW) children. AIM: To investigate whether cerebral MRI pathology relates to different types of neuroimpairments in adolescents with VLBW. METHODS: At age 15, 55 adolescents with birth weight < or = 1500 g (VLBW) were examined. Motor function was evaluated by Movement Assessment Battery for Children (ABC) and the Grooved Pegboard (GP) test, cognitive function by Wechsler Intelligence Scales, and visuo-motor and visual perceptual function by The Developmental Test of Visual-Motor Integration (VMI) with the supplementary tests of Visual Perception (VP), and Motor Coordination (MC). Executive functions were assessed by Wisconsin Card Sorting Test (WCST) and the Stroop test. Cerebral MRI was assessed semi-quantitatively for ventricular, white and grey matter pathology. RESULTS: There was a rather weak relationship between MRI pathology and neuroimpairments. Poor performance on the WCST was related with ventricular dilatation (VD), white matter reduction and corpus callosum thinning. There was a correlation between results on the VMI test and the Movement ABC test and MRI pathology, but the correlation became much weaker when children with cerebral palsy were excluded. There was no relationship between MRI findings and estimated intelligence quotient (IQ) scores. Normal MRI predicted normal or near normal neuropsychological functioning. CONCLUSION: Cerebral MRI pathology suggestive of perinatal white matter injury was related to disadvantages in performances on executive functions, to a lesser degree to motor and visual perceptual problems, but not to cognitive impairments in VLBW adolescents.

MR guided cancer treatment system for an elevated therapeutic index - a macroscopic approach.

Adjuvant therapy for cancer usually refers to surgery followed by chemotherapy and/or radiation treatment to decrease the risk of recurrence. But still, the absolute benefit for survival obtained with adjuvant therapy compared with control is only approximately 6%. The objective of this analysis is to formulate a non-invasive multimodal cancer treatment system related to cancer stem cells and hypoxic fractions of solid tumors, emphasizing MRI monitoring and guidance, to elevate the therapeutic index. Tumor hypoxia is a therapeutic concern since it can reduce the effectiveness of drugs and radiotherapy, where well oxygenated cells requiring one third of the dose of hypoxic cells to achieve a given level of cell killing. Cancer stem cells might be the cause of tumor recurrence, sometimes many years after the appearance of the successful treatment of a primary tumor. Thus, the primary objective of such a treatment system will be to provide sufficient selective toxicity to both kill cancer stem cells and cells of hypoxic fractions of the tumor. Active tumor targeting with the use of liposomally encapsulated drugs is the starting point of the treatment procedure. The system facilitates quality assurance means by MR monitoring of drug accumulation and drug release, in real time. Cavitation involves the nucleation, growth and oscillation of gaseous cavities. Selective drug release and/or hyperthermia are achieved by ultrasound induced cavitation well defined to the tumor region. Hyperthermic effects, increased vascularization and subsequent increase in pO2 levels to hypoxic regions, can be monitored by MRI. MRI monitoring of key physiological parameters facilitates optimization related to approximate real time concomitant treatments, including correct timing and various combinations of drug therapy, hyperthermia, ionizing radiation, ablation, other treatment options, before or after surgery. The likelihood of an improved therapeutic index with the use of such a system seems compelling. Further research related to optimal timing, combinations of responses between liposomally encapsulated drug dosage, ultrasound exposure, hyperthermia, pO2 response time, ionizing radiation fractionation and treatment time, have to be conducted.

Multimodal ultrasound mediated drug release model in local cancer therapy.

Increased cancer survival rates over the last decades are probably less due to advances of a single treatment modality than to optimization of adjuvant treatment procedures. The efficiency of drug delivery in solid tumours is crucial for achieving local tumour control as cytotoxic agents do not target cancer cells selectively. To enhance tumour uptake and selectivity of drugs, liposomally encapsulated microbubbles with drugs or temperature sensitive liposomes with therapeutics have been suggested as new drug delivery vehicles, in combination with ultrasound or hyperthermia, respectively. The presented release model goes beyond simple drug delivery or traditional adjuvant therapies. It represents targeting, real time monitoring and imaging, and exerts concurrent application of therapeutic modalities, within a multimodal treatment regime, thus enhancing synergism. An appropriate diagnostic tool is applied to determine the region of interest with respect to reference coordinates. The delineated region of interest can be modelled by topographic modelling techniques. A subsequent adequate digital tumour model can facilitate an optimal treatment procedure. The system integrates a diagnostic unit with a therapeutic ultrasonic transmitting component, together with a central processing unit, encompassing algorithms for data processing and visualization. Actual drug uptake is based on passive accumulation of drug carriers. Selective drug release of e.g. cytostatic drugs is achieved by ultrasound induced cavitation well defined to the tumour region. Monitoring of drug release can be achieved by imaging techniques. Measurement and monitoring of cavitational activities within the volume of release, and established functional relationships between cavitation level and drug release, will be bridged to various control functions by the processing unit. Further concurrent thermal treatment approaches and ionizing radiation modi are proposed within the comprehensive treatment model. The described multimodal treatment concept has been converted into an actual patient treatment system, and further elucidated into a concrete algorithm for the therapy of patients. Image guided drug release, mediated by focused ultrasound, within a multimodal treatment framework, may localize the effects to the tumour volume and, therefore, allowing for more aggressive therapy, thus enhancing the therapeutic ratio. Integrated image guided drug release systems will probably increase treatment efficacy and survival rates in the future.

Differentiating prospective control information for catching in at-risk and control adolescents.

This paper investigated the use of prospective control in catching and how the results can be used as a sensitive tool to detect diffuse signs of brain dysfunction. A detailed analysis of 286 catching movements of eight adolescents (two males, six females [four very-low-birth weight {VLBW}, one small for gestational age {SGA}, and three appropriate for gestational age]; mean age 14 y 5 mo [SD 6 mo]; range 14-15 y) was performed blind for this purpose. The moving target approached the participants from the side at three different, non-constant accelerations. The results showed that three adolescents used less advanced timing strategies that involved the lower-order variables of distance or velocity to govern movement initiation of at least one of their hands. Two of these were preterm VLBW and one was term SGA. The remaining adolescents, on the other hand, all relied on the higher-order variable of time-to-contact to initiate their hand movements, and were, therefore, considered low-risk. These results were compared with the cerebral magnetic resonance imaging results of the adolescents. The findings show that timing strategy pinpoints successfully those adolescents at risk of neurological problems. It was, therefore, concluded that the skill of using prospective information for catching can be used as a tool to detect diffuse signs of motor dysfunction, which are not readily detected by standard behavioural tests alone.

Cerebral metabolite differences in adolescents with low birth weight: assessment with in vivo proton MR spectroscopy.

BACKGROUND: Children with very low birth weight (VLBW) have a significantly increased risk of later neurodevelopmental problems, while infants born small for gestational age (SGA) at term are also at some risk of developing neurological impairment. OBJECTIVE: To investigate possible brain metabolite differences in adolescents with VLBW, SGA at term and controls by proton in vivo magnetic resonance spectroscopy (MRS) at 1.5 T. MATERIALS AND METHODS: MR spectra were acquired from volumes localized in the left frontal lobe, containing mainly white matter (54 subjects). Peak areas of N-acetyl aspartate (NAA), choline (Cho) and creatine (Cr) were determined, and the peak area ratio of NAA to Cr, total Cho to Cr, or NAA to Cho calculated. Probabilistic neural network (PNN) analysis was performed utilizing the chemical shift region containing resonances from NAA, Cho and Cr as inputs. RESULTS: No significant difference in the peak area ratios could be found using the Kruskal-Wallis test. By application of PNN, a correct classification of 52 of the 54 adolescents with a sensitivity and specificity exceeding 93% for all groups was achieved. CONCLUSION: Small, yet systematic, differences in brain metabolite distribution among the groups were confirmed by PNN analysis.

Magnetic resonance imaging analysis of bioabsorbable interference screws used for fixation of bone-patellar tendon-bone autografts in endoscopic reconstruction of the anterior cruciate ligament.

BACKGROUND: Metal interference screws can cause problems if revision is needed and can interfere with magnetic resonance imaging. Bioabsorbable screws have been developed to prevent these problems, but the rate of resorption and integration is not well understood. HYPOTHESIS: Poly-L-lactic acid interference screws will be resorbed 2 years after anterior cruciate ligament reconstruction. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The study group consisted of 19 patients with isolated anterior cruciate ligament ruptures reconstructed with bone-patellar tendon-bone autografts fixed with poly-L-lactic acid interference screws using an endoscopic technique. Magnetic resonance imaging was used to evaluate resorption of the screws, bony integration of the screws, and integration of the bone blocks after 2 years. RESULTS: At 2 years, the mean reduction in the volume of the femoral screws was 64% and of the tibial screw was 63%. Bony integration of the femoral bone block was considered good in 17 patients and fair in 2 patients. Integration of the tibial bone block was considered good in 16 patients and fair in 1 patient who demonstrated widening of the tibial tunnel. Osteolysis around the screws was seen in 3 patients in the femur and none in the tibia. CONCLUSION: The mean reduction in volume of the poly-L-lactic acid screws as measured by magnetic resonance imaging after 2 years was approximately two thirds. The integration of the bone blocks was considered good in 90% of the patients. Osteolysis around the screws was visible in 16% of the patients. CLINICAL RELEVANCE: Two years after ACL reconstruction using poly-L-lactic acid interference screws, the surgeon can expect to find approximately one third of the volume of the screw remaining in the bone tunnels.

Synergistic and tumour selective effects of chemotherapy and ultrasound treatment.

In the present work, we have analysed the effects of low frequency ultrasound exposure in combination with liposomally encapsulated doxorubicin (Caelyx) and Plurogel encapsulated fluorouracil (5-FU) on 144 Balb/c nude mice inoculated with a WiDr (human colon cancer) tumour cell line, at various concentrations. Furthermore, the theoretical foundation for the effects of ultrasound exposure of tissues and organs, and for its interaction with and enhancement of controlled release of encapsulated anticancer drugs are outlined. For the first time, it is shown that non-hyperthermic ultrasound treatment significantly increases the effect of liposomally encapsulated cytostatic drugs on tumour growth. Synergetic effects were larger for low drug concentrations, indicating that the approach may benefit patients for whom chemotherapeutic treatment gives limited effect, or for whom drug concentrations have to be restricted due to general health considerations.

Low-birth-weight adolescents: psychiatric symptoms and cerebral MRI abnormalities.

To explore associations between psychiatric symptoms and cerebral magnetic resonance imaging abnormalities in low-birth-weight adolescents, 55 very low-birth-weight (or=10th centile) were assessed at 14-15 years of age. Outcome measures were Schedule for Affective Disorders and Schizophrenia for School-Age Children, Attention-Deficit/Hyperactivity Disorder Rating Scale IV, Autism Spectrum Screening Questionnaire, and qualitatively assessed cerebral magnetic resonance images. The very low-birth-weight group manifested increased prevalence of psychiatric symptoms and disorders compared with controls (P < 0.001), especially symptoms of attention-deficit/hyperactivity disorder, and high frequency of ventricular dilatation, white matter reduction, thinning of corpus callosum, and gliosis (P < 0.01 vs controls). The Attention-Deficit/Hyperactivity Disorder Rating Scale score was significantly associated with white matter reduction and thinning of corpus callosum in this group. The term small for gestational age group had increased prevalence of psychiatric symptoms compared with control subjects, but not more frequent abnormalities on cerebral magnetic resonance imaging. In conclusion, attention-deficit/hyperactivity disorder symptoms were significantly associated with white matter reduction and thinning of corpus callosum in very low-birth-weight adolescents. No associations were found for other psychiatric symptoms and brain abnormalities in any of the groups.

Degeneration and height of cervical discs classified from MRI compared with precise height measurements from radiographs.

STUDY DESIGN: Descriptive study comparing MRI classifications with measurements from radiographs. OBJECTIVES: 1. Define the relationship between MRI classified cervical disc degeneration and objectively measured disc height. 2. Assess the level of inter- and intra-observer errors using MRI in defining cervical disc degeneration. SUMMARY OF BACKGROUND DATA: Cervical spine degeneration has been defined radiologically by loss of disc height, decreased disc and bone marrow signal intensity and disc protrusion/herniation on MRI. The intra- and inter-observer error using MRI in defining cervical degeneration influences data interpretation. Few previous studies have addressed this source of error. The relation and time sequence between cervical disc degeneration classified by MRI and cervical disc height decrease measured from radiographs is unclear. METHODS: The MRI classification of degeneration was based on nucleus signal, prolaps identification and bone marrow signal. Two neuro-radiologists evaluated the MR-images independently in a blinded fashion. The radiographic disc height measurements were done by a new computer-assisted method compensating for image distortion and permitting comparison with normal level-, age- and gender-appropriate disc height. RESULTS/CONCLUSIONS: 1. Progressing disc degeneration classified from MRI is on average significantly associated with a decrease of disc height as measured from radiographs. Within each MRI defined category of degeneration measured disc heights, however, scatter in a wide range. 2. The inter-observer agreement between two neuro-radiologists in both defining degeneration and disc height by MRI was only moderate. Studies addressing questions related to cervical disc degeneration should take this into consideration.

Cerebral MRI findings in very-low-birth-weight and small-for-gestational-age children at 15 years of age.

BACKGROUND: A high prevalence of abnormal cerebral MRI findings has been reported in low-birth-weight children. OBJECTIVE: To compare MRI findings in very-low-birth-weight (VLBW) and term small-for-gestational-age (SGA) children with controls in early adolescence. MATERIALS AND METHODS: Cerebral MRI was used to examine 55 VLBW, 54 SGA and 66 controls at 15 years of age. The MR images were qualitatively assessed, and size of ventricles, white-matter and grey-matter abnormalities were reported. RESULTS: The VLBW teenagers had a higher prevalence of various MRI abnormalities than SGA children and controls. Dilation of the ventricular system, especially of the occipital horns, was found in 82% of the VLBW group, in 19% of the SGA group and in 21% of controls. White-matter reduction was found in 53% of the VLBW, in 6% of the SGA and in 2% of controls. Corpus callosum thinning was found in 47% of the VLBW, in 2% of the SGA and in 6% of controls. Periventricular gliosis was found in 29% of the VLBW, in 4% of the SGA and in 8% of controls. CONCLUSIONS: Cerebral MRI pathology in white matter is a common finding in VLBW teenagers. The findings may indicate minor perinatal PVL with resulting loss of white-matter tissue and ventricular dilation.