UK Lung Cancer RCT Pilot Screening Trial: baseline findings from the screening arm provide evidence for the potential implementation of lung cancer screening.

BACKGROUND: Lung cancer screening using low-dose CT (LDCT) was shown to reduce lung cancer mortality by 20% in the National Lung Screening Trial. METHODS: The pilot UK Lung Cancer Screening (UKLS) is a randomised controlled trial of LDCT screening for lung cancer versus usual care. A population-based questionnaire was used to identify high-risk individuals. CT screen-detected nodules were managed by a pre-specified protocol. Cost effectiveness was modelled with reference to the National Lung Cancer Screening Trial mortality reduction. RESULTS: 247 354 individuals aged 50-75 years were approached; 30.7% expressed an interest, 8729 (11.5%) were eligible and 4055 were randomised, 2028 into the CT arm (1994 underwent a CT). Forty-two participants (2.1%) had confirmed lung cancer, 34 (1.7%) at baseline and 8 (0.4%) at the 12-month scan. 28/42 (66.7%) had stage I disease, 36/42 (85.7%) had stage I or II disease. 35/42 (83.3%) had surgical resection. 536 subjects had nodules greater than 50 mm(3) or 5 mm diameter and 41/536 were found to have lung cancer. One further cancer was detected by follow-up of nodules between 15 and 50 mm(3) at 12 months. The baseline estimate for the incremental cost-effectiveness ratio of once-only CT screening, under the UKLS protocol, was £8466 per quality adjusted life year gained (CI £5542 to £12 569). CONCLUSIONS: The UKLS pilot trial demonstrated that it is possible to detect lung cancer at an early stage and deliver potentially curative treatment in over 80% of cases. Health economic analysis suggests that the intervention would be cost effective-this needs to be confirmed using data on observed lung cancer mortality reduction. TRIAL REGISTRATION: ISRCTN 78513845.

Systemic hypothermia in acute cervical spinal cord injury: a case-controlled study.

INTRODUCTION: Systemic hypothermia remains a promising neuroprotective strategy. There has been recent interest in its use in patients with spinal cord injury (SCI). In this article, we describe our extended single center experience using intravascular hypothermia for the treatment of cervical SCI. METHODS: Thirty-five acute cervical SCI patients received modest (33 °C) intravascular hypothermia for 48 h. Neurological outcome was assessed by the International Standards for Neurological Classification of Spinal Cord Injury scale (ISNCSCI) developed by the American Spinal Injury Association. Local and systemic complications were recorded. RESULTS: All patients were complete ISNCSCI A on admission, but four converted to ISNCSCI B in <24 h post injury. Hypothermia was delivered in 5.76 (±0.45) hours from injury if we exclude four cases with delayed admission (>18 h). Fifteen of total 35 patients (43%) improved at least one ISNCSCI grade at latest follow up 10.07 (±1.03) months. Even excluding those patients who converted from ISNCSCI A within 24 h, 35.5% (11 out of 31) improved at least one ISNCSCI grade. Both retrospective (n=14) and prospective (n=21) groups revealed similar number of respiratory complications. The overall risk of any thromboembolic complication was 14.2%. CONCLUSION: The results are promising in terms of safety and improvement in neurological outcome. To date, the study represents the largest study cohort of cervical SCI patients treated by modest hypothermia. A multi-center, randomized study is needed to determine if systemic hypothermia should be a part of SCI patients' treatment for whom few options exist.

Comparing the functional representations of central and border whiskers in rat primary somatosensory cortex.

The anatomical representations of the large facial whiskers, termed barrels, are topographically organized and highly segregated in the posteromedial barrel subfield (PMBSF) of rat layer IV primary somatosensory cortex. Although the functional representations of single whiskers are aligned with their appropriate barrels, their areal extents are rather large, spreading outward from the appropriate barrel along the tangential plane and thereby spanning multiple neighboring and non-neighboring barrels and septal regions. To date, single-whisker functional representations have been characterized primarily for whiskers whose corresponding barrels are located centrally within the PMBSF (central whiskers). Using intrinsic signal imaging verified with post-imaging single-unit recording, we demonstrate that border whiskers, whose barrels are located at the borders of the PMBSF, also evoke large activity areas that are similar in size to those of central whiskers but spread beyond the PMBSF and sometimes beyond primary somatosensory cortex into the neighboring dysgranular zones. This study indicates that the large functional representation of a single whisker is a basic functional feature of the rat whisker-to-barrel system and, combined with results from other studies, suggest that a large functional representation of a small, point-like area on the sensory epithelium may be a functional feature of primary sensory cortex in general.

The electrochemical evaluation of a Zr-based bulk metallic glass in a phosphate-buffered saline electrolyte.

Bulk metallic glasses (BMGs) represent an emerging class of materials with an amorphous structure and a unique combination of properties. The objectives of this investigation were to define the electrochemical behavior of a specific Zr-based BMG alloy in a physiologically relevant environment and to compare these properties to standard, crystalline biomaterials as well as other Zr-based BMG compositions. Cyclic-anodic-polarization studies were conducted with a Zr52.5Cu17.9Ni14.6Al10.0Ti5.0 (at %) BMG in a phosphate-buffered saline electrolyte with a physiologically relevant oxygen content at 37 degrees C. The results were compared to three common, crystalline biomaterials: CoCrMo, 316L stainless steel, and Ti-6Al-4V. The BMG alloy was found to have a lower corrosion penetration rate (CPR), as compared to the 316L stainless steel, and an equivalent CPR, as compared to the CoCrMo and Ti-6Al-4V alloys. Furthermore, the BMG alloy demonstrated better localized corrosion resistance than the 316L stainless steel. However, the localized corrosion resistance of the BMG alloy was not as high as those of the CoCrMo and Ti-6Al-4V alloys in the tested environment. The excellent electrochemical properties demonstrated by the BMG alloy are combined with a low modulus and unparalleled strength. This unique combination of properties dramatically demonstrates the potential for amorphous alloys as a new generation of biomaterials.

Contribution of the DDDD motif of H. influenzae e (P4) to phosphomonoesterase activity and heme transport.

Haemophilus influenzae lipoprotein e (P4) is a member of the DDDD phosphohydrolase superfamily and mediates heme transport. Each of the aspartate residues of the signature motif is required for phosphomonoesterase activity, as none of the e (P4) single D mutants (D64A, D66A, D181N, and D185A) possessed detectable phosphomonoesterase activity. These results suggest that the signature motif is essential to the phosphomonoesterase activity of lipoprotein e (P4). When assessed for phosphomonoesterase-dependent heme transport activity in Escherichia coli hemA strains, plasmids containing D181N and D185A retained heme transport as indicated by aerobic growth while D64A and D66A did not. We conclude that phosphomonoesterase activity is not required for heme transport.

MR characterization of brain and brain tumor response to radiotherapy.

This paper describes our experience in using the T1 and T2 relaxation times for quantitative evaluation of brain and brain tumor response to radiation therapy. Twenty-two computed T1 and 22 computed T2 images were obtained from 66 routine inversion-recovery and spin-echo magnetic resonance (MR) brain scans. The relaxation times of the brain tissues, determined from the computed images, were examined as a function of the absorbed dose. Statistical evaluation of the results showed no significant difference between the relaxation times of irradiated and not irradiated tissues, including tumor and normal white matter. Influence of the magnetic field strength and imaging techniques on the computed T1 and T2 values was confirmed. We conclude that the relaxation time values, as obtained today using conventional MR scanner and standard software, are not specific enough to warrant a correct assessment of the acute radiation effect on the brain tissues.

Hypothermia in spinal cord injury.

Early investigations involving central nervous system (CNS) temperature lowering to protect against the detrimental effects of hypoxia and ischemia were based on the observation that hypothermia reduces brain metabolism and energy consumption. The protective effects of hypothermia have been demonstrated in numerous experimental models of cerebral ischemia and recently in models of brain trauma. These observations also led to the application of hypothermia, in the form of local spinal cord cooling (LSCC), in animal models of experimental spinal cord injury (SCI). Although some investigators have reported negative results in studies of LSCC following traumatic SCI, the majority of studies have noted beneficial effects. The favorable results in animal experimentation led to a limited number of cases where LSCC was used in the treatment of human SCI. However, results are difficult to interpret because (1) most investigators report only a small number of cases, (2) the studies lack a control population, (3) the time interval from injury to the application of cooling has been highly variable, and (4) several investigators combined drug treatments with LSCC. In these experiments, LSCC was achieved via perfusion with a cold solution or an epidural heat exchanger and the aim was to lower cord temperatures significantly (about 10 degrees C). The application of the technique itself is fraught with difficulties. It requires acute surgery in a traumatized patient, a wide multilevel laminectomy, and minimizing the time interval between injury and the application of spinal cord cooling. Recent studies in experimental brain ischemia strongly suggest that a drastic lowering of CNS temperature may be unnecessary to lessen the degree of tissue damage occurring following an ischemic brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuroprotective effects of basic fibroblast growth factor following spinal cord contusion injury in the rat.

Cytokines and neurotrophic factors have been implicated in the pathophysiology of injury to the central nervous system. While some cytokines are considered pro-inflammatory, other factors promote neuronal growth and survival. The present study investigated the neuroprotective effects of interleukins 1 (IL-1), 4 (IL-4), and 6 (IL-6), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and basic fibroblast growth factor (bFGF) in a contusion model of spinal cord injury. Female Sprague-Dawley rats (n = 55) sustained a 10-g weight-drop injury to the lower thoracic spinal cord (T10) from a height of 12.5 mm using the NYU impactor. A micro-infusion system (Alzet minipump) was used to continuously deliver drugs or vehicle directly into the epicenter of the contused spinal cord starting 1 or three h postinjury. At the end of 7 days, animals were perfused and the cords removed for histopathological analysis. Longitudinal serial sections were cut on a freezing microtome and stained with cresyl violet. Areas of central necrosis, partial preservation, and total zone of tissue injury were identified and traced by an independent reviewer using a computer based imaging system. The mean total zone of injury in five animals receiving vehicle infusion was 18.04+/-4.20 mm3. The mean zone of partial preservation in these animals was 16.46+/-3.32 mm. Basic fibroblast growth factor reduced the total zone of injury by 33% [p<0.01, least significant difference (LSD) of Fisher] in five animals and the zone of partial preservation by 32% (p<0.01, LSD of Fisher) when compared to controls. There were trends toward reduction in total zone of injury and zone of partial preservation in rats treated with IL-4, CNTF, and NGF versus vehicle; however, none of these reached statistical significance. No significant differences were observed between animals receiving vehicle versus bFGF treatment commencing 3 h after injury. These data demonstrate that the continuous intramedullary infusion of bFGF initiated one hour after moderate contusion injury of the spinal cord significantly reduces the total zone of injury and the zone of partial preservation. These results support the further investigation and possible future clinical application of bFGF in the treatment of acute spinal cord contusion injury.

Dorsal spinal venous occlusion in the rat.

Occlusion of the major components of the spinal venous system is usually associated with spinal arteriovenous malformations or systemic thrombophlebitis. Although spinal venous system dysfunction has been implicated in compressive cord syndromes, myelopathies from decompression sickness, and spinal cord trauma, its pathophysiology remains unclear. To characterize disorders associated with spinal venous occlusion, we developed a model in the rat produced by focally coagulating the dorsal spinal vein transdurally at the T7 and T10 vertebral levels. Following such occlusion, venous stasis, sludging and perivascular hemorrhages in the small venous branches were observed. By 1 week postocclusion, animals developed hindlimb paralysis from which they partially recovered over time. Histologic examination in the acute phase disclosed tissue necrosis, edema, and hemorrhages predominantly in the dorsal aspect of the spinal cord. This was gradually replaced by an intense macrophagic infiltration and the partial formation of a cystic cavity by 1 month. These findings indicate that dorsal spinal vein occlusion in the rat causes significant neurologic and pathologic alterations. We conclude that this procedure produces a relevant animal model for the study of the pathophysiology of spinal venous occlusion, and it allows the characterization of its effects on spinal cord blood flow, the blood-spinal cord barrier, and the development of edema independent of cord compression. Our findings in this model provide an insight into one of the mechanisms of injury extension in spinal cord trauma and other disorders associated with spinal venous dysfunction.

Replacing residents with midlevel practitioners: a New York City-area analysis.

Reducing the number of residency positions in U.S. teaching hospitals poses special problems for New York City-area hospitals, which rely heavily on residents to deliver patient care services. This study analyzes the costs of replacing residents with midlevel practitioners under proposals considered in 1994 by Congress to limit the number of first-year training positions and alter the configuration of primary care physicians and specialists produced. The study found that, depending on the replacement strategy used, the proposals could require New York City-area hospitals to hire thousands of midlevel practitioners and other staff, costing a minimum of $242 million annually, to cover patient care services.

Photochemically induced spinal cord injury in the rat.

We have developed in the rat a minimally invasive model of reproducible spinal cord injury initiated photochemically. With the exposed spinal column intact, 560 nm irradiation of the translucent dorsal surface induces excitation of the systemically injected dye, rose Bengal, in the spinal cord microvasculature. The resultant photochemical reaction leads to vascular stasis. Histopathological changes at 7 days include hemorrhagic necrosis of the central gray matter, edematous pale-staining white matter tracts and vascular congestion. At the level of cord irradiation (T8) the entire cord thickness is necrosed except for the periphery of the anterior funiculus. Voluntary motor function is consistently lost in the subacute phase of injury.

Somatosensory evoked potential measurements in percutaneous fluid aspiration from intraspinal cystic lesions.

Two patients were evaluated with somatosensory evoked potentials (SSEPs) before and after CT-guided fluid aspiration from cystic intraspinal lesions. Our objective was to use the information and the clinical response to this procedure to determine the suitability of the patients for surgical intervention. In both patients, one with a pseudomeningocele and the other with a subarachnoid cyst, improvement in their symptoms corresponded to significant changes in their SSEPs. We believe this technique may be useful in selected cases when it is unclear whether cystic intraspinal fluid collections are responsible for the patient's symptoms. An increase in amplitude and/or decrease in latency of SSEPs, along with clinical improvement after fluid aspiration, may indicate the potential benefit of surgical intervention.

Progressive posttraumatic myelomalacic myelopathy: imaging and clinical features.

PURPOSE: To describe the imaging features, surgical management, and clinical outcome of progressive posttraumatic myelomalacic myelopathy (PPMM), a relatively unrecognized but important cause of progressive myelopathy in patients with previous spinal cord injuries. METHODS: The clinical records, imaging studies, and postoperative outcome of 10 patients with PPMM were reviewed. Fifteen preoperative and five postoperative MRs were analyzed for intramedullary signal abnormalities, the nature of these signal abnormalities, and cord tethering. All patients had intraoperative sonography. RESULTS: Neurologic signs and symptoms found in our patients included 1) progressive loss of motor function (6/10), 2) sensory level changes (4/10), 3) increased spasticity (4/10), 4) autonomic dysreflexia (4/10), 5) loss of bowel or bladder control (4/10), and 6) local and/or radicular pain (4/10). Preoperative MR in nine patients revealed intramedullary T1/T2 lengthening (9/9), extramedullary tethering/adhesions (9/9), ill-defined lesional borders (6/9), cord expansion (5/9), and increased signal intensity of the lesion on T1-weighted images compared with CSF (7/9). Proton density images in five patients demonstrated a relative increase in signal intensity over CSF. In all five postoperative MRs, there was evidence of untethering of the spinal cord and a decrease in cord size in two patients. Intraoperative sonography revealed cord tethering and abnormal cord echotexture in all cases. Postoperative clinical evaluation revealed neurologic improvement in nine patients. CONCLUSIONS: PPMM may clinically and radiographically mimic progressive posttraumatic cystic myelopathy (PPCM). MR provides clues to the diagnosis of myelomalacia preoperatively. Intraoperative sonography confirms the absence of a confluent cyst. These points are crucial in the surgical procedures in PPMM vs PPCM. In PPMM, lysis of intradural adhesions results in an improvement in symptoms in a manner similar to the shunting of PPCM.

Radiologic evaluation of spinal cord fissures.

The clinical course and radiographic studies were reviewed of eight patients with posttraumatic spinal cord fissures (rents in the spinal cord communicating with the subarachnoid space). Five patients had spinal cord fissures associated with symptomatic intramedullary cysts that required shunting to alleviate progressive neurologic deficits and intractable pain. Their metrizamide myelograms showed contrast medium passing immediately from the subarachnoid sac into the spinal cord and their immediate metrizamide CT scans delineated the entire extent of the secondary cord cysts. Intraoperative sonography confirmed the presence of the cord fissures with sizeable cysts, detected adhesions, and guided myelotomies and the subsequent shunting and collapse of the cysts. Since neurologic improvement followed the shunting procedures in all five patients treated for progressive symptoms, it was concluded that early radiologic evaluation of posttraumatic spinal cord fissures with symptomatic cord cysts is crucial in the clinical management of these patients.

Acquired spinal subarachnoid cysts: evaluation with MR, CT myelography, and intraoperative sonography.

Fifteen patients with acquired spinal subarachnoid cysts (14 surgically proved, one presumed) were evaluated preoperatively with immediate and/or delayed CT myelography (seven patients), MR (11 patients), or both (three patients). CT myelography separated subarachnoid cyst from myelomalacia and/or intramedullary cysts in four cases but failed to diagnose them in three, while MR accurately diagnosed subarachnoid cyst in all 10 cases that were also surgically proved. The results of these preoperative examinations were evaluated to determine the efficacy of each study in diagnosing subarachnoid cysts, ascertaining their extent and internal architecture, and detecting associated abnormalities of the spinal cord. In addition, during surgery these cysts were studied with sonography to gain an understanding of the pathophysiological mechanisms involved in their formation and propagation and to guide the surgeon in their decompression. On the basis of our experience, MR appears to be the most efficient preoperative study in diagnosing and characterizing acquired subarachnoid cyst and associated abnormalities. Intraoperative sonography provides a reliable means of ensuring adequate decompression of these cysts.

Spinal dural arteriovenous fistulas: evaluation with MR angiography.

PURPOSE: To show that postgadolinium three-dimensional time-of-flight MR angiography shows abnormal intradural vessels associated with spinal dural arteriovenous fistula better than routine MR imaging and provides screening information useful for subsequent diagnostic conventional angiography and/or posttreatment evaluation. METHODS: Precontrast and postcontrast MR imaging and MR angiograms, as well as subsequent digital subtraction angiograms, were obtained for eight patients with dural arteriovenous fistulas, diagnosed with digital subtraction angiography and verified with surgery. In four patients, MR studies also were obtained after surgery. RESULTS: All patients had cord hyperintensity of T2-weighted images and postgadolinium enhancement on T1-weighted images. Five had vessellike signal abnormalities in the subarachnoid space on MR. Abnormal intradural vessels were detected in all eight patients with MR angiography. Comparison with digital subtraction angiography revealed these vessels to be primarily enlarged veins of the coronal venous plexus on the cord surface. In six patients, the medullary vein draining the fistula was demonstrated, indicating the level of the fistula, later identified by digital subtraction angiography. After surgical obliteration of the fistula, the draining medullary vein and most or all of the abnormal coronal veins were no longer demonstrated, with decrease or resolution of cord hyperintensity on T2-weighted images. CONCLUSION: Postgadolinium, spinal MR angiography in cases of suspected dural arteriovenous fistula provides information about intradural veins that supplements the diagnostic value of the MR imaging results, facilitates the subsequent digital subtraction angiography study, and, in treated cases, reflects the success of surgery and/or embolization.

Lumbar disk herniation and canal stenosis: value of intraoperative sonography in diagnosis and surgical management.

One-hundred-four patients with preoperative diagnoses of lumbar canal stenosis, disk herniation, or a combination of both were evaluated with intraoperative sonography with the intent of (1) describing the sonographic characteristics of herniated disks and distinguishing these from bulging anuli, epidural fat, scar tissue, and spondylolisthesis; (2) establishing criteria for adequate decompression of canal stenosis; and (3) determining the usefulness of sonography in monitoring disk removal. Disk material demonstrates medium echogenicity, different in its sonographic features from bone, epidural fat, scar tissue, and epidural veins. A sonographic diagnosis of disk herniation was made in 43 cases, 41 of which were confirmed during surgery. Sonography established the presence or absence of disk herniation (confirmed by surgery) in 14 of 19 patients who had equivocal preoperative findings. After routine diskectomy, residual disk material was found in 17 (41%) of 41 patients, which led to further surgery in 16 patients with removal of the additional disk fragments. In 84 patients undergoing decompressive surgery for canal stenosis, sonography detected residual canal compression in 19 (23%), which led to a widened decompression in 15 of these patients. Sonography can differentiate disk material from other normal or abnormal structures in the canal; therefore, sonographic monitoring helps to ensure adequate bony decompression and complete diskectomy. We conclude that intraoperative sonography is an important tool in the surgical management of lumbar disk disease and stenosis.

Continuity and discontinuity models of bulimia nervosa: a taxometric investigation.

Past research evaluating the continuity and discontinuity models of bulimia has produced inconclusive results. In the current study, we performed a taxometric analysis of bulimia nervosa using means above minus below a sliding cut and maximum covariance analysis with a sample of women diagnosed with bulimia nervosa (n = 201) or women college students (n = 412). Indicators were derived from the Bulimia Test--Revised and the Eating Attitudes Test--26, and both a mixed sample and the nonclinical sample were analyzed. With both taxometric methods and both mixed and nonclinical samples, results were consistently suggestive of a latent taxon for bulimia. These results challenge a dimensional model of bulimia nervosa.

Computer-assisted fluoroscopic targeting system for pedicle screw insertion.

OBJECTIVE: Biplanar fluoroscopic imaging linked to a computer-driven mechanical end-effector is under development as a targeting system for spinal surgery. This technology has the potential to enhance standard intraoperative fluoroscopic information for localization of the pedicle entry point and trajectory, and it may be an effective alternative to the computed tomography-based image-guided system (IGS) in pedicle screw placement. A preclinical study to assess the accuracy and time efficiency of this system versus a conventional IGS was conducted. METHODS: Pedicle screw placement was performed in six cadavers from T1 to S1 levels using the ViewPoint IGS (Picker International, Inc., Cleveland, OH) on one side versus the Fluorotactic guidance system (Z-Kat, Inc., Miami, FL) on the other side. Of 216 possible pedicles, 208 were instrumented; 8 pedicle diameters were too small or were not adequately imaged. Postinsertion, each pedicle was assessed for the presence and location of cortical perforation using computed tomographic scanning and direct visualization. RESULTS: The number of successful screw placements was 89 (87.3%) of 102 for IGS and 87 (82.1 %) of 106 for the Fluorotactic guidance system, respectively. The mean time to register and operate on one level using the Fluorotactic guidance system was 14:34 minutes (minutes:seconds), compared with 6:50 minutes using the IGS. The average fluoroscope time was 4.6 seconds per pedicle. CONCLUSION: Our data indicate that this first-generation fluoroscopy-based targeting system can significantly assist the surgeon in pedicle screw placement. The overall accuracy is comparable to an IGS, especially in the region of T9-L5. A second-generation system with a faster end-effector and user-friendly interface should significantly reduce the operating and fluoroscope time.

Comparison of stability provided to the unstable spine by the kinetic therapy table and the Stryker frame.

Loss of spinal alignment can lead to neurological compromise in individuals with unstable spine injuries. We compared the ability of the Roto-Rest bed and the Stryker frame to immobilize an unstable cervical and lumbar segment in a cadaver. The Roto-Rest bed was superior to the Stryker frame in the immobilization of both cervical and lumbar fractures.