Mapping at the nanometer scale the effects of sea-salt derived chlorine on cinnabar and lead white by using delayed image extraction in ToF-SIMS.

In this work, an innovative analytical approach focused on the use of advanced imaging techniques for the chemical mapping of degradation and/or restoration products is proposed. A representative cross-section showing a very complex stratigraphy from the Saint Wilgefortis Triptych (Hieronymus Bosch), exhibited in the Galleria dell'Accademia di Venezia, was investigated. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) experiments were performed using a time-of-flight detector operating in the so-called delayed extraction mode. The time delay applied during the extraction of the secondary ions permitted mass spectra to be obtained with an excellent mass resolution and chemical maps with nanometer scale spatial resolution. The painting's cross-section was also analysed at the micrometer scale by micro-Fourier transform infrared spectroscopy (micro-FTIR). The combined analytical approaches highlighted the colocalization of lead chloride, oxychloride, and hydroxychloride ions, suggesting the transformation of lead white ((PbCO3)2Pb(OH)2) into laurionite (PbClOH). Furthermore, chlorine appears evenly diffused in the cinnabar (HgS) layer, inducing the alteration of its more external part into calomel (Hg2Cl2). In fact, from the chemical maps the presence in the sample of an unaltered portion of the cinnabar layer is evident. Such degradation products were probably due to the exposure of the painting to a chloride-rich atmosphere for a long time. This led to a global blackening of the painting. To protect the painting from aggressive chemical species, siloxane compounds were probably used as a modern restorative treatment. ToF-SIMS chemical maps revealed permeation of the silicon-based consolidants within the sample's cracks and no interaction products with the other constitutive materials of the painting were found. Finally, the presence of different lead soaps was detected in correspondence with the lead white layer.

Two phase 3, multicenter, randomized, placebo-controlled clinical trials of fampridine-SR for treatment of spasticity in chronic spinal cord injury.

STUDY DESIGN: Two randomized, double-blind, placebo-controlled trials. OBJECTIVE: To evaluate the efficacy and safety of fampridine sustained-release tablets (fampridine-SR) 25 mg twice daily for moderate-to-severe spasticity in patients with chronic spinal cord injury (SCI). SETTING: United States and Canada. METHODS: Patients with incomplete chronic SCI were randomized to twice daily fampridine-SR 25 mg or placebo, with a 2-week single-blind placebo run-in, a 2-week titration, 12 weeks of stable dosing, 2 weeks of downward titration and 2 weeks of untreated follow-up. Co-primary end points were the change from baseline, averaged over the double-blind treatment period, for Ashworth score (bilateral knee flexors and extensors) and a 7-point Subject Global Impression of treatment (SGI; 1, terrible; 7, delighted). Secondary end points were: Penn Spasm Frequency Scale; the motor/sensory score from the International Standards for Neurological Classification of SCI; Clinician's Global Impression of Change of neurological status; and the International Index of Erectile Function (men) or the Female Sexual Function Index (women). RESULTS: The populations were 212 and 203 patients in the two studies, respectively. Changes from baseline in Ashworth score were -0.15 (placebo) and -0.19 (fampridine-SR) in the first study, and -0.16 (placebo) and -0.28 (fampridine-SR) in the second study. The between-treatment difference was not significant for either the Ashworth score or the SGI and, with few exceptions, neither were the secondary end points. Fampridine-SR was generally well tolerated; treatment-emergent adverse events (TEAEs) and serious TEAEs were reported with similar frequency between treatments. CONCLUSION: Fampridine-SR was well tolerated. No significant differences were observed between treatment groups for the primary end points of Ashworth score and SGI.

Long-term adherence to first-line highly active antiretroviral therapy in a hospital-based cohort: predictors and impact on virologic response and relapse.

A high level of adherence to highly active antiretroviral therapy (HAART) is essential to minimize the risk of treatment failure and HIV disease progression. This cohort study evaluated the prevalence and predictors of long-term adherence with first-line HAART in a hospital-based unselected sample of HIV patients from central Italy, and examined the association between adherence and virological response or relapse. Between July 1996 and June 2004, 171 patients (67.3% males; mean age, 41.2 years) were followed for at least 24 weeks and up to 8 years. Adherence was measured by patient self-reports and confirmed using pharmacy records. The prevalence of high-level adherence (>or=90%) at 6 months was 88.3%; slightly less than 80% at 12 months. The incidence of adherence failure in the sample remained fairly stable until 24 months of follow-up, then it declined about 5% every 6 months. Cox analysis showed that compared to single/separated patients, homeless and married persons were, respectively, 1.95 times more likely and two times less likely to experience adherence failure (p < 0.05). The adjusted risk of adherence failure among patients who did not suffer drug-related toxicity was 0.57 (p < 0.05). Medication adherence was significantly associated with shorter time to virological response and longer time to relapse. Adherents were 1.69 times more likely to achieve viral suppression and nine times less likely to experience relapse than nonadherents (p < 0.01). Efforts at improving adherence should be prolonged for at least 24 months. A protective role of marriage for adherence failure is promising but requires confirmation in further research, that should also clarify the exact mechanisms determining the association.

Glass-ceramic coated Mg-Ca alloys for biomedical implant applications.

Biodegradable metals and alloys are promising candidates for biomedical bone implant applications. However, due to the high rate of their biodegradation in human body environment, they should be coated with less reactive materials, such, for example, as bioactive glasses or glass-ceramics. Fort this scope, RKKP composition glass-ceramic coatings have been deposited on Mg-Ca(1.4wt%) alloy substrates by Pulsed Laser Deposition method, and their properties have been characterized by a number of techniques. The prepared coatings consist of hydroxyapatite and wollastonite phases, having composition close to that of the bulk target material used for depositions. The 100µm thick films are characterized by dense, compact and rough morphology. They are composed of a glassy matrix with various size (from micro- to nano-) granular inclusions. The average surface roughness is about 295±30nm due to the contribution of micrometric aggregates, while the roughness of the fine-texture particulates is approximately 47±4nm. The results of the electrochemical corrosion evaluation tests evidence that the RKKP coating improves the corrosion resistance of the Mg-Ca (1.4wt%) alloy in Simulated Body Fluid.

Silver-Doped Calcium Phosphate Bone Cements with Antibacterial Properties.

Calcium phosphate bone cements (CPCs) with antibacterial properties are demanded for clinical applications. In this study, we demonstrated the use of a relatively simple processing route based on preparation of silver-doped CPCs (CPCs-Ag) through the preparation of solid dispersed active powder phase. Real-time monitoring of structural transformations and kinetics of several CPCs-Ag formulations (Ag = 0 wt %, 0.6 wt % and 1.0 wt %) was performed by the Energy Dispersive X-ray Diffraction technique. The partial conversion of ß-tricalcium phosphate (TCP) phase into the dicalcium phosphate dihydrate (DCPD) took place in all the investigated cement systems. In the pristine cement powders, Ag in its metallic form was found, whereas for CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt % cements, CaAg(PO3)3 was detected and Ag (met.) was no longer present. The CPC-Ag 0 wt % cement exhibited a compressive strength of 6.5 ± 1.0 MPa, whereas for the doped cements (CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt %) the reduced values of the compressive strength 4.0 ± 1.0 and 1.5 ± 1.0 MPa, respectively, were detected. Silver-ion release from CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt % cements, measured by the Atomic Emission Spectroscopy, corresponds to the average values of 25 µg/L and 43 µg/L, respectively, rising a plateau after 15 days. The results of the antibacterial test proved the inhibitory effect towards pathogenic Escherichia coli for both CPC-Ag 0.6 wt % and CPC-Ag 1.0 wt % cements, better performances being observed for the cement with a higher Ag-content.

Neurological assessment in spinal cord injury.

Precise and reliable neurologic assessment is a necessary tool for determining the extent and pattern of recovery after SCI. Recently agreed upon international standards establish a uniform neurologic classification to measure clinical outcomes. They are currently in use in three multicenter studies in more than 40 SCI centers in the United States. The Model System SCI centers report the use of these measures, such as impairment grades and neurologic levels, in almost 15,000 cases over the past 20 years and, more recently, motor scores in 3,500 patients. The NASCIS II multicenter trial on methylprednisolone used motor and sensory scores as endpoints in close to 500 patients, but have incorporated the international standards, which include a disability measure, in NASCIS III. The study of ganglioside effectiveness also is using these measures in many patients. In more focused studies, neurologic assessment soon after injury can predict walking in motor complete injuries based on pin prick sensation, and in motor incomplete injuries based on impairment grade and age. Eventual upper extremity function can be estimated based on the motor examination within 72 hours of injury. Both the motor score and motor level are more reliable in predicting upper extremity function than the single sensory level. This presumably reflects the greater importance of motor recovery on functional outcome. The proximal muscles of the lower extremities caudal to the lesion site recover before distal muscles, and this may be mediated by axons descending in the ventral tracts, which control primarily proximal rather than distal muscles. These axons may be preferentially spared and/or have greater capacity to compensate than those present in the lateral columns. In conclusion, standard neurologic assessment in SCI is extremely valuable in monitoring recovery in order to prognosticate functional outcome, evaluate effectiveness of drug interventions, and provide valuable clues to possible underlying mechanisms of recovery. The elucidation of these mechanisms will aid in the refinement of current treatments and development of new strategies to enhance neurologic recovery and functional outcome.

Prognostic significance of the delayed plantar reflex following spinal cord injury.

The delayed plantar reflex (DPR) is a pathologic flexor variant which requires unusually strong stimulation of the sole of the foot and is characterized by a prolonged interval between the stimulus and the response, slow and protracted plantarflexion of the great toe and/or other toes and slow return to the neutral position. The purpose of this study was to evaluate prospectively the functional outcome of spinal cord injury (SCI) patients based on the presence or absence of a DPR immediately following injury. Thirty-six subjects were evaluated within one week of injury. A complete neurological evaluation following American Spinal Injury Association (ASIA) standards was performed and the presence or absence of a DPR was noted on admission. Ambulation status and ASIA Impairment Scales were recorded at discharge from the rehabilitation unit and the data were analyzed by the Chi-square method with Yates' correction for continuity. The data demonstrated a high correlation of the DPR with motor complete injuries (p < 0.01) and a poor prognosis for recovery of ambulation (p < 0.01). Clinicians should recognize this abnormal reflex, which may be used in conjunction with a complete neurological examination, to help prognosticate future function in the acute SCI patient.

Phase 2 trial of sustained-release fampridine in chronic spinal cord injury.

STUDY DESIGN: Double-blind, randomized, placebo-controlled, parallel-group clinical trial. OBJECTIVE: Assess safety and efficacy of sustained-release fampridine in subjects with chronic spinal cord injury. SETTING: A total of 11 academic rehabilitation research centers in the United States. METHODS: A total of 91 subjects with motor-incomplete spinal cord injury (SCI), randomized to three arms: fampridine, sustained release, 25 mg b.i.d. (Group I), 40 mg b.i.d. (Group II), and placebo (Group III) for 8 weeks. OUTCOME MEASURES: Patient diary questionnaire, Ashworth score, American Spinal Cord Injury Association International Standards, International Index of Erectile Function, bladder and bowel management questionnaires, and Clinician and Subject Global Impressions (Clinician Global Impression of change, Subject Global Impression (SGI)). Safety was evaluated from adverse events, physical examinations, vital signs, electrocardiograms, and laboratory tests. RESULTS: In total, 78% of the subjects completed the study. More (13/30) discontinued from Group II than Group I (4/30) and Group III (3/31). The most frequent adverse events across groups were hypertonia, generalized spasm, insomnia, dizziness, asthenia, pain, constipation, and headache. One subject in Group II experienced a seizure. SGI changed significantly in favor of Group I (P=0.02). Subgroup analysis of subjects with baseline Ashworth scores >1 showed significant improvement in spasticity in Group I versus III (P=0.02). CONCLUSIONS: Group I showed significant improvement in SGI, and potential benefit on spasticity. The drug was well tolerated. Group II showed more adverse events and discontinuations.

Neuromuscular disease: rehabilitation and electrodiagnosis. 1. Anatomy and physiology of nerve and muscle.

This article of the Self-Directed Physiatric Education Program to assist practitioners and trainees in physical medicine and rehabilitation identifies the anatomy and physiology of nerve, neuromuscular junction, and muscle as they relate to rehabilitation of diseases affecting these structures. Structural relationships of the spinal roots, peripheral nerves, motor units, and muscle fibers are outlined, with structural, functional, and electrodiagnostic correlations. Features of nerve and muscle biochemistry and physiology are reviewed as they relate to common neurological diseases, age, and sex. The spontaneous potentials, motor unit activities, and nerve conduction abnormalities found in diseases of nerve and muscle also are described.

Spinal cord injury syndrome with motor sparing in the absence of all sensation.

This paper describes the anatomic basis for the unusual presentation in a spinal cord injured subject of preservation of motor power in the absence of all sensation. The patient was examined at four hours, and daily thereafter, after a motorcycle accident in which he was thrown over the handle bars. He had trace ankle dorsi and plantar flexors, but light touch, pin, position, and vibratory sensation were absent below the level of C4 bilaterally. There was no physical evidence to differentiate whether he suffered a flexion or extension injury. Cervical spine films showed no evidence of fracture or dislocation, but anterior and posterior osteophytes involving C3 to C4, C4 to C5, and C5 to C6 were present. Magnetic resonance imaging showed evidence of cervical cord edema at C3 to C4 with possible hemorrhage and severe spinal stenosis at C3 to C4 and C4 to C5. This patient received a compression injury with resulting classic anterior spinal artery syndrome. Because of his spinal stenosis with a decreased anterior-posterior (AP) diameter of the canal, the posterior circulation was also compromised. The extensive pial anastomotic network provided relative sparing of the most peripheral components of the lateral corticospinal tracts. This case report demonstrates a unique clinical picture that cannot be anatomically classified by current American Spinal Injury Association (ASIA) standards as central cord syndrome. It can be explained by the lamination of the ascending and descending tracts in relation to the vascular supply of the cervical cord in conjunction with the narrowing of the AP diameter of the canal due to spinal stenosis.

Spinal cord injury: prognosis for ambulation based on sensory examination in patients who are initially motor complete.

The purpose of this retrospective study was to document that patients with motor complete injury, but preserved pin appreciation, in addition to light touch, below the zone of injury have better prognoses with regard to ambulation than patients with only light touch preserved. Medical records were examined of all spinal cord injury (SCI) patients admitted between 1982 and 1988. Twenty-seven Frankel B patients with upper motor neuron lesions admitted within 72 hours of injury were identified. These patients were divided into two groups (B-1 and B-2). Group B-1 (n = 18) were patients who had touch sensation but no pin appreciation below the zone of injury. Group B-2 (n = 9) were patients who had partial or complete pin appreciation and light touch below the zone of injury. The charts were examined for the patient's ability to walk independently using a reciprocal gait for at least 200 feet. The data were analyzed by the Fisher Exact test. Eight of the nine Group B-2 patients ambulated as compared to two of the 18 Group B-1 patients (p less than .0002). Frankel B SCI patients with only touch preserved below the zone of injury had poor prognoses for ambulation; those with preserved pin appreciation below the zone of injury had excellent prognoses to regain functional ambulation.

Neuromuscular disease: rehabilitation and electrodiagnosis. 2. Nerve disease.

The purpose of this section of the Self-Directed Physiatric Education Program Study Guide on rehabilitation in diseases affecting nerve and muscle is to assist practitioners and trainees in physical medicine and rehabilitation by providing an overview of the evaluation, treatment, and rehabilitative care of patients with inherited and acquired neuropathies. Both diffuse and focal processes are discussed. Current research is briefly reviewed, and the utility and limitations of electrodiagnostic studies are discussed.

Recovery of ambulation in motor-incomplete tetraplegia.

OBJECTIVE: To determine the effect of age and initial neurologic status on recovery of ambulation in patients with motor-incomplete tetraplegia. STUDY DESIGN: Inception cohort study. SETTING: Urban, tertiary care hospital with Regional Spinal Cord Injury Center. PATIENTS: One hundred five patients with American Spinal Injury Association (ASIA) C or D tetraplegia at admission or within 72 hours of injury. MAIN OUTCOME MEASURE: Ambulatory status at time of discharge from inpatient rehabilitation. RESULTS: Ninety-one percent (30/33) of ASIA C patients younger than 50 years of age became ambulatory by discharge, versus 42% (13/31) ASIA C patients age 50 or older (p < .0001). All (41/41) patients initially classified as ASIA D became ambulatory by discharge. CONCLUSION: For patients with ASIA D tetraplegia, prognosis for recovery of independent ambulation is excellent. For patients with ASIA C tetraplegia, recovery of ambulation is significantly less likely if age is 50 years or older.

The pattern of reflex recovery during spinal shock.

STUDY DESIGN: A prospective descriptive study of the course of recovery of reflexes following acute spinal cord injury (SCI). OBJECTIVES: The purpose of the study was to observe the pattern of reflex recovery following acute SCI in order to determine the prognostic significance of reflexes for ambulation and their relationship to spinal shock. SETTING: A regional spinal cord injury center in Philadelphia, Pennsylvania, USA. METHODS: Fifty subjects admitted consecutively over a 9 month period and on the day of injury were observed for the following reflexes; bulbo-cavernosis (BC), delayed plantar response (DPR), cremasteric (CRM), ankle jerk (AJ), knee jerk (KJ), and normal plantar response for 5 7 days a week and 6-8 weeks duration. The 50 subjects were assessed for ambulation of 200 feet at time of discharge. MRI studies were reviewed on 13/28 complete (ASIA A) injuries. RESULTS: Thirty-five subjects (28 ASIA A, 4 ASIA B, 3 ASIA C) had a DPR of 2 days or longer duration and these subjects were not ambulatory. The fourteen subjects (12 ASIA D and 2 ASIA C), who were ambulatory, either had no DPR (11/14) or had a DPR of only 1 days duration (3/14). One subject (ASIA B) was not ambulatory and had a DRP of 1 days duration. The DPR was the first reflex to recover most often, followed by the BC, CRM in the first few days and later followed by the deep tendon reflexes (AJ & KJ) by 1-2 weeks respectively. Less than 8% of subjects had no reflexes on the day of injury and the reflexes did not follow a caudal-rostral pattern of recovery. CONCLUSIONS: Prognosis for ambulation based on reflexes early after SCI should not be linked to current descriptions of spinal shock. In fact, the view of spinal shock, based on the absence of reflexes and the recovery of reflexes in a caudal to rostral sequence, is of limited clinical utility and should be discarded. The evolution of reflexes over several days following injury may be more relevant to prognosis than the use of the term spinal shock and the presence or absence of reflexes on the day of injury.

Spinal cord injury: prognosis for ambulation based on quadriceps recovery.

The purpose of this study was to determine if early recovery of quadricep muscle strength post spinal cord injury (SCI) is a useful predictor of future ambulation. Seventeen C4-T10 motor incomplete (Frankel C) spinal cord injured patients admitted to our center between March 1988 and April 1990 were examined within 72 hours to one week post injury. All patients had initial quadricep strengths < or = 2/5 in both legs. Strength in the strongest quadricep was followed prospectively at intervals from admission to one year post injury. Recovery time to a > 3/5 quadricep was established for each patient. Patients were categorized into 2 groups: FA (n = 11) were those patients who achieved functional ambulation and NA (n = 6) were those subjects who were nonambulators. Functional ambulators were defined as those patients who were able to walk in the household and/or the community while non ambulators were those who either did not ambulate or did so only for exercise. All patients (n = 9) who achieved a > 3/5 quadricep by 2 months post SCI became functional ambulators whereas in the group of 8 patients who did not achieve a > 3/5 by 2 months, only 2 became functional ambulators. This result was found to be significant using a point-by-serial correlation with p < 0.05. In conclusion, motor incomplete spinal cord injured patients who recovered to a > 3/5 quadricep strength by 2 months post injury had an excellent prognosis for subsequent ambulation by 6 months post injury.

Walking index for spinal cord injury (WISCI): an international multicenter validity and reliability study.

STUDY DESIGN: Construction of an international walking scale by a modified Delphi technique. OBJECTIVE: The purpose of the study was to develop a more precise walking scale for use in clinical trials of subjects with spinal cord injury (SCI) and to determine its validity and reliability. SETTING: Eight SCI centers in Australia, Brazil, Canada (2), Korea, Italy, the UK and the US. METHODS: Original items were constructed by experts at two SCI centers (Italy and the US) and blindly ranked in an hierarchical order (pilot data). These items were compared to the Functional Independence Measure (FIM) for concurrent validity. Subsequent independent blind rank ordering of items was completed at all eight centers (24 individuals and eight teams). Final consensus on rank ordering was reached during an international meeting (face validation). A videotape comprised of 40 clips of patients walking was forwarded to all eight centers and inter-rater reliability data collected. RESULTS: Kendall coefficient of concordance for the pilot data was significant (W=0. 843, P<0.001) indicating agreement among the experts in rank ordering of original items. FIM comparison (Spearman's rank correlation coefficient=0.765, P<0.001) showed a theoretical relationship, however a practical difference in what is measured by each scale. Kendall coefficient of concordance for the international blind hierarchical ranking showed significance (W=0.860, P<0.001) indicating agreement in rank ordering across all eight centers. Group consensus meeting resulted in a 19 item hierarchical rank ordered 'Walking Index for Spinal Cord Injury (WISCI)'. Inter-rater reliability scoring of the 40 video clips showed 100% agreement. CONCLUSIONS: This is the first time a walking scale for SCI of this complexity has been developed and judged by an international group of experts. The WISCI showed good validity and reliability, but needs to be assessed in clinical settings for responsiveness.