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1.
Mater Sci Eng C Mater Biol Appl ; 98: 118-124, 2019 May.
Article in English | MEDLINE | ID: mdl-30813002

ABSTRACT

We report a plasma immersion ion implantation process for functionalizing polymer coated magnetic particles, converting them into a universal covalent binding platform for the simultaneous binding of multiple molecular agents without the need for specialised chemical linking groups. As an example, we demonstrate the improvement of wettability and the control of surface charge of polystyrene coated magnetic particles, enhancing biomolecule attachment density with strong covalent binding. We demonstrate the preparation of multifunctional magnetic particles where two or more types of molecule are co-immobilized. This enables a platform technology with simultaneous multiple covalent binding of molecules drawn from oligonucleotides, antibodies and enzymes suitable for targeted nanoparticle diagnostic and therapies.


Subject(s)
Antibodies/chemistry , Nanoparticles/chemistry , Oligonucleotides/chemistry , Polystyrenes/chemistry , Polymers/chemistry , Surface Properties , Wettability
2.
Neurourol Urodyn ; 37(1): 385-393, 2018 01.
Article in English | MEDLINE | ID: mdl-28666061

ABSTRACT

AIMS: A proof of principle study of a novel wearable device to control neurogenic detrusor over-activity in eight male spinal cord injured subjects using conditional neuromodulation. METHODS: Transrectal stimulation was delivered through the device in response to simultaneously recorded external anal sphincter (EAS) contraction as a marker for neurogenic detrusor overactivity (NDO). The effect of conditional neuromodulation on bladder capacity and maximum detrusor pressure was investigated in addition to reliability of dyssynergic sphincter contraction as a marker for NDO. RESULTS: Conditional neuromodulation through the novel device showed a statistically significant increase in bladder capacity and reduction in maximum detrusor pressure in six male subjects with spinal cord injury (SCI). EAS activity was a reliable surrogate for detection of NDO. CONCLUSIONS: It has been shown for the first time that conditional neuromodulation can be delivered and triggered via a single biocompatible device placed in the anal canal. The pudendal nerves lying in Alcock's canal were stimulated through the wall of the anal canal, and the dyssynergic activity of the EAS was used to detect NDO and trigger neuromodulation giving significant increases in bladder capacity and reduction in detrusor pressure in six male subjects with SCI.


Subject(s)
Spinal Cord Injuries/complications , Urinary Bladder, Neurogenic/therapy , Urinary Bladder, Overactive/therapy , Adolescent , Adult , Aged , Humans , Male , Middle Aged , Muscle Contraction/physiology , Reproducibility of Results , Transcutaneous Electric Nerve Stimulation , Treatment Outcome , Urinary Bladder, Neurogenic/etiology , Urinary Bladder, Overactive/etiology , Young Adult
3.
Physiol Meas ; 38(11): L17-L27, 2017 Oct 31.
Article in English | MEDLINE | ID: mdl-28901946

ABSTRACT

OBJECTIVE: Conditional trans-rectal stimulation of the pudendal nerve could provide a viable solution to treat hyperreflexive bladder in spinal cord injury. A set threshold of the amplitude estimate of the external anal sphincter surface electromyography (sEMG) may be used as the trigger signal. The efficacy of such a device should be tested in a large scale clinical trial. As such, a probe should remain in situ for several hours while patients attend to their daily routine; the recording electrodes should be designed to be large enough to maintain good contact while observing design constraints. The objective of this study was to arrive at a design for intra-anal sEMG recording electrodes for the subsequent clinical trials while deriving the possible recording and processing parameters. APPROACH: Having in mind existing solutions and based on theoretical and anatomical considerations, a set of four multi-electrode probes were designed and developed. These were tested in a healthy subject and the measured sEMG traces were recorded and appropriately processed. MAIN RESULTS: It was shown that while comparatively large electrodes record sEMG traces that are not sufficiently correlated with the external anal sphincter contractions, smaller electrodes may not maintain a stable electrode tissue contact. It was shown that 3 mm wide and 1 cm long electrodes with 5 mm inter-electrode spacing, in agreement with Nyquist sampling, placed 1 cm from the orifice may intra-anally record a sEMG trace sufficiently correlated with external anal sphincter activity. SIGNIFICANCE: The outcome of this study can be used in any biofeedback, treatment or diagnostic application where the activity of the external anal sphincter sEMG should be detected for an extended period of time.


Subject(s)
Anal Canal/physiology , Electromyography/instrumentation , Electrodes , Equipment Design , Muscles/physiology , Signal-To-Noise Ratio
4.
Microbiologyopen ; 5(3): 413-23, 2016 06.
Article in English | MEDLINE | ID: mdl-26860427

ABSTRACT

S-type pyocins are bacteriocins produced by Pseudomonas aeruginosa isolates to antagonize or kill other strains of the same species. They have a modular organization comprising a receptor-binding domain recognizing a surface constituent of the target bacterium, a domain for translocation through the periplasm, and a killing or toxic domain with DNase, tRNase, or pore-forming activity. Pyocins S2, S3, S4, and S5 recognize TonB-dependent ferri-siderophore receptors in the outer membrane. We here describe a new nuclease bacteriocin, pyocin S6, encoded in the genome of a P. aeruginosa cystic fibrosis (CF) clinical isolate, CF_PA39. Similarly to pyocins S1 and S2, the S6 toxin-immunity gene tandem was recruited to the genomic region encoding exotoxin A. The pyocin S6 receptor-binding and translocation domains are identical to those of pyocin S1, whereas the killing domain is similar to the 16S ribonuclease domain of Escherichia coli colicin E3. The cytotoxic activity was abolished in pyocin S6 forms with a mutation in the colicin E3-equivalent catalytic motif. The CF_PA39 S6 immunity gene displays a higher expression level than the gene encoding the killing protein, the latter being only detected when bacteria are grown under iron-limiting conditions. In the S1-pyocinogenic strain P. aeruginosa ATCC 25324 and pyocin S2 producer P. aeruginosa PAO1, a remnant of the pyocin S6 killing domain and an intact S6-type immunity gene are located downstream of their respective pyocin operons. Strain PAO1 is insensitive for pyocin S6, and its S6-type immunity gene provides protection against pyocin S6 activity. Purified pyocin S6 inhibits one-fifth of 110 P. aeruginosa CF clinical isolates tested, showing clearer inhibition zones when the target cells are grown under iron limitation. In this panel, about half of the CF clinical isolates were found to host the S6 genes. The pyocin S6 locus is also present in the genome of some non-CF clinical isolates.


Subject(s)
Anti-Bacterial Agents/pharmacology , Cystic Fibrosis/microbiology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/pathogenicity , Pyocins/pharmacology , Amino Acid Sequence , Anti-Bacterial Agents/chemistry , Bacterial Outer Membrane Proteins/metabolism , Bacteriocins/genetics , Base Sequence , Cloning, Molecular , Escherichia coli/genetics , Escherichia coli/metabolism , Humans , Microbial Sensitivity Tests , Protein Structure, Tertiary , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Pyocins/chemistry , Pyocins/immunology , RNA, Ribosomal, 16S/genetics , RNA, Ribosomal, 16S/metabolism
5.
IEEE Trans Neural Syst Rehabil Eng ; 24(4): 506-15, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26415182

ABSTRACT

After spinal cord injury, functions of the lower urinary tract may be disrupted. A wearable device with surface electrodes which can effectively control the bladder functions would be highly beneficial to the patients. A trans-rectal pudendal nerve stimulator may provide such a solution. However, the major limiting factor in such a stimulator is the high level of current it requires to recruit the nerve fibers. Also, the variability of the trajectory of the nerve in different individuals should be considered. Using computational models and an approximate trajectory of the nerve derived from an MRI study, it is demonstrated in this paper that it may be possible to considerably reduce the required current levels for trans-rectal stimulation of the pudendal nerve compared to the values previously reported in the literature. This was corroborated by considering an ensemble of possible and probable variations of the trajectory. The outcome of this study suggests that trans-rectal stimulation of the pudendal nerve is a plausible long term solution for treating lower urinary tract dysfunctions after spinal cord injury.


Subject(s)
Action Potentials , Algorithms , Models, Neurological , Pudendal Nerve/physiopathology , Therapy, Computer-Assisted/methods , Transcutaneous Electric Nerve Stimulation/instrumentation , Computer Simulation , Electric Conductivity , Equipment Design , Equipment Failure Analysis , Humans , Transcutaneous Electric Nerve Stimulation/methods , Urinary Bladder/innervation , Wireless Technology/instrumentation
6.
Neurourol Urodyn ; 34(4): 349-55, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25867009

ABSTRACT

AIMS: To reveal the effectiveness of corticospinal drive in facilitating the pudendal reflex in the anal sphincter muscle, as a surrogate marker for the urethral sphincter, in incomplete spinal cord injury (iSCI). METHODS: Three neurologically normal subjects and twenty-six subjects with incomplete, supra-sacral spinal cord injuries and symptoms of a neuropathic bladder were recruited. Incontinence was assessed using the International Consultation on Incontinence Modular Questionnaire (ICIQ). Electromyographic activity of the external anal sphincter was recorded. The pudendo-anal reflex (PAR) was elicited by electrical stimulation of the dorsal penile nerve (DPN). Motor cortical excitation was achieved using transcranial magnetic stimulation (TMS). RESULTS: Preliminary findings in normal and iSCI subjects showed facilitation of the PAR by prior TMS with an optimal interval of 20-40 msec. Of 23 iSCI subjects, 12 showed facilitation to TMS applied 30 msec before DPN stimulation. Eight of the 12, and a further five iSCI subjects, had an anal sphincter MEP in response to TMS alone. There was a weak tendency (r(2) = 0.22, P = 0.03) for those with higher ICIQ values to have larger PAR responses but no significant difference in ICIQ scores between those with (ICIQ = 4.9 ± 4.0 mean ± SD) and those without (ICIQ = 7.2 ± 4.7) cortical facilitation of the PAR. CONCLUSIONS: Cortical TMS was effective in facilitating the PAR in some iSCI subjects. The presence of cortical facilitation of the PAR was not related to the degree of urinary continence.


Subject(s)
Anal Canal/innervation , Pudendal Nerve/physiopathology , Pyramidal Tracts/physiopathology , Reflex , Spinal Cord Injuries/physiopathology , Urinary Incontinence/physiopathology , Adult , Aged , Case-Control Studies , Electromyography , Humans , Male , Middle Aged , Pilot Projects , Spinal Cord Injuries/complications , Spinal Cord Injuries/diagnosis , Surveys and Questionnaires , Transcranial Magnetic Stimulation , Treatment Outcome , Urinary Incontinence/diagnosis , Urinary Incontinence/etiology , Urinary Incontinence/therapy
7.
Article in English | MEDLINE | ID: mdl-24904326

ABSTRACT

Cortical and spinal cord plasticity may be induced with non-invasive transcranial magnetic stimulation to encourage long term potentiation or depression of neuronal circuits. Such plasticity inducing stimulation provides an attractive approach to promote changes in sensorimotor circuits that have been degraded by spinal cord injury (SCI). If residual corticospinal circuits can be conditioned appropriately there should be the possibility that the changes are accompanied by functional recovery. This article reviews the attempts that have been made to restore sensorimotor function and to obtain functional benefits from the application of repetitive transcranial magnetic stimulation (rTMS) of the cortex following incomplete spinal cord injury. The confounding issues that arise with the application of rTMS, specifically in SCI, are enumerated. Finally, consideration is given to the potential for rTMS to be used in the restoration of bladder and bowel sphincter function and consequent functional recovery of the guarding reflex.

8.
Pathog Dis ; 71(1): 26-38, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24659602

ABSTRACT

Chronic Pseudomonas aeruginosa infections are the main cause of morbidity among patients with cystic fibrosis (CF) due to persistent lung inflammation caused by interaction between this bacterium and the immune system. Longitudinal studies of clonally related isolates of a dominant CF clone have indicated that genome reduction frequently occurs during adaptation of P. aeruginosa in the CF lung. In this study, we have evaluated the P. aeruginosa population structure of patients attending the Universitair Ziekenhuis Brussel (UZ Brussel) CF reference center using a combination of genotyping methods. Although the UZ Brussel P. aeruginosa CF population is characterized by the absence of a dominant CF clone, some potential interpatient transmissions could be detected. Interestingly, one of these clones showed deletion of the alternative type I ferripyoverdine receptor gene fpvB. Furthermore, we found that several other TonB-dependent receptors are deleted as well. The genome of one potentially transmissible CF clone was sequenced, revealing large deleted regions including all type III secretion system genes and several virulence genes. Remarkably, a large number of deleted genes are shared between the P. aeruginosa CF clone described in this study and isolates belonging to the dominant Copenhagen CF DK2 clone, suggesting parallel evolution.


Subject(s)
Adaptation, Biological , Cystic Fibrosis/complications , Membrane Proteins/deficiency , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/isolation & purification , Sequence Deletion , Adolescent , Adult , Bacterial Proteins , Belgium , Child , Cystic Fibrosis/microbiology , Female , Genes, Bacterial , Humans , Male , Middle Aged , Molecular Sequence Data , Sequence Analysis, DNA , Young Adult
9.
Microbiology (Reading) ; 160(Pt 2): 261-269, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24217175

ABSTRACT

Pyocins are toxic proteins produced by some strains of Pseudomonas aeruginosa that are lethal for related strains of the same species. Some soluble pyocins (S2, S3 and S4) were previously shown to use the pyoverdine siderophore receptors to enter the cell. The P. aeruginosa PAO1 pore-forming pyocin S5 encoding gene (PAO985) was cloned into the expression vector pET15b, and the affinity-purified protein product tested for its killing activity against different P. aeruginosa strains. The results, however, did not show any correlation with a specific ferripyoverdine receptor. To further identify the S5 receptor, transposon mutants were generated. Pooled mutants were exposed to pyocin S5 and the resistant colonies growing in the killing zone were selected. The majority of S5-resistant mutants had an insertion in the fptA gene encoding the receptor for the siderophore pyochelin. Complementation of an fptA transposon mutant with the P. aeruginosa fptA gene in trans restored the sensitivity to S5. In order to define the receptor-binding domain of pyocin S5, two hybrid pyocins were constructed containing different regions from pyocin S5 fused to the C-terminal translocation and DNase killing domains of pyocin S2. Only the protein containing amino acid residues 151 to 300 from S5 showed toxicity, indicating that the pyocin S5 receptor-binding domain is not at the N-terminus of the protein as in other S-type pyocins. Pyocin S5 was, however, unable to kill Burkholderia cenocepacia strains producing a ferripyochelin FptA receptor, nor was the B. cenocepacia fptA gene able to restore the sensitivity of the resistant fptA mutant P. aeruginosa strain.


Subject(s)
Bacterial Outer Membrane Proteins/metabolism , Microbial Viability/drug effects , Pseudomonas aeruginosa/drug effects , Pyocins/metabolism , Pyocins/toxicity , Receptors, Cell Surface/metabolism , Burkholderia cenocepacia/drug effects , Burkholderia cenocepacia/genetics , DNA Mutational Analysis , DNA Transposable Elements , Gene Knockout Techniques , Genetic Complementation Test , Mutagenesis, Insertional , Protein Interaction Mapping , Pseudomonas aeruginosa/genetics , Pseudomonas aeruginosa/physiology , Pyocins/isolation & purification
10.
Sci Transl Med ; 5(210): 210ra155, 2013 Nov 06.
Article in English | MEDLINE | ID: mdl-24197736

ABSTRACT

A severe complication of spinal cord injury is loss of bladder function (neurogenic bladder), which is characterized by loss of bladder sensation and voluntary control of micturition (urination), and spontaneous hyperreflexive voiding against a closed sphincter (detrusor-sphincter dyssynergia). A sacral anterior root stimulator at low frequency can drive volitional bladder voiding, but surgical rhizotomy of the lumbosacral dorsal roots is needed to prevent spontaneous voiding and dyssynergia. However, rhizotomy is irreversible and eliminates sexual function, and the stimulator gives no information on bladder fullness. We designed a closed-loop neuroprosthetic interface that measures bladder fullness and prevents spontaneous voiding episodes without the need for dorsal rhizotomy in a rat model. To obtain bladder sensory information, we implanted teased dorsal roots (rootlets) within the rat vertebral column into microchannel electrodes, which provided signal amplification and noise suppression. As long as they were attached to the spinal cord, these rootlets survived for up to 3 months and contained axons and blood vessels. Electrophysiological recordings showed that half of the rootlets propagated action potentials, with firing frequency correlated to bladder fullness. When the bladder became full enough to initiate spontaneous voiding, high-frequency/amplitude sensory activity was detected. Voiding was abolished using a high-frequency depolarizing block to the ventral roots. A ventral root stimulator initiated bladder emptying at low frequency and prevented unwanted contraction at high frequency. These data suggest that sensory information from the dorsal root together with a ventral root stimulator could form the basis for a closed-loop bladder neuroprosthetic.


Subject(s)
Neural Prostheses , Prosthesis Design , Spinal Cord Injuries/physiopathology , Urinary Bladder/physiopathology , Action Potentials , Animals , Axons/pathology , Electric Stimulation , Female , Implants, Experimental , Microelectrodes , Myelin Sheath/metabolism , Nerve Block , Organ Size , Rats , Rats, Sprague-Dawley , Spinal Nerve Roots/blood supply , Spinal Nerve Roots/physiopathology , Spinal Nerve Roots/surgery , Urination
11.
Spine J ; 13(12): 1818-25, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23954558

ABSTRACT

BACKGROUND CONTEXT: Despite the significant interest in the assessment of human cerebral perfusion, investigations into human spinal cord perfusion (SCP) are scarce. Current intraoperative monitoring of spinal cord relies on the assessment of neural conduction as a surrogate for SCP. However, there are various inherent limitations associated with the use of these techniques. Near infrared spectroscopy (NIRS) has been successfully used for monitoring and assessment of human cerebral perfusion and has shown promising results in intraoperative assessment of SCP in animal models. PURPOSE: The aim of this study was to investigate whether it is possible to monitor physiological changes in human SCP intraoperatively using NIRS with indocyanine green (ICG) tracer technique. We used this technique to calculate the human spinal cord carbon dioxide (CO2) reactivity index. In addition, we investigated whether the lamina causes significant attenuation of NIRS signals. STUDY DESIGN/SETTING: Intraoperative human experimental study. PATIENT SAMPLE: Eighteen patients undergoing elective posterior cervical spine surgery. OUTCOME MEASURES: Carbon dioxide reactivity of human SCP. METHODS: Nine patients underwent transdural assessment of SCP, with an additional nine patients undergoing translaminar measurements. Patients' SCP was continuously monitored using an NIRO-500 NIRS monitor via a set of purpose built optodes. Their arterial ICG concentration was simultaneously assessed using a pulse dye densitometer. Patients' end-tidal CO2 was gradually increased by 7.5 mm Hg and then returned back to baseline. Three sets of measurements were taken: baseline, hypercapnic, and return to baseline. RESULTS: After hypercapnia, SCP increased by a mean of 57.2 ± 23.3% in the transdural group and 46.6 ± 36.3% in the translaminar group. Carbon dioxide reactivity index was 7.6 ± 3.2%ΔSCP/mm Hg in the transdural group and 6.4 ± 5.3 %ΔSCP/mm Hg in the translaminar group. There was no significant difference in the increase in SCP (p=.475) or the CO2 reactivity index (p=.581) observed between the transdural and the translaminar groups. CONCLUSIONS: Intraoperative NIRS with ICG tracer technique can identify an increase in the SCP in response to hypercapnia. It is possible to use this technique for monitoring SCP over the dura and the lamina. This technique could potentially be used to provide insight in to the pathophysiology and autoregulation of commonly acquired spinal cord conditions. Further research assessing the use of NIRS for monitoring of SCP is required.


Subject(s)
Intraoperative Neurophysiological Monitoring/methods , Spectroscopy, Near-Infrared/methods , Spinal Cord/blood supply , Aged , Carbon Dioxide/analysis , Carbon Dioxide/metabolism , Female , Humans , Indocyanine Green , Male , Middle Aged
12.
Handb Clin Neurol ; 109: 247-57, 2012.
Article in English | MEDLINE | ID: mdl-23098717

ABSTRACT

The principles of using electrical stimulation of peripheral nerves or nerve roots for restoring useful bladder, bowel, and sexual function after damage or disease of the central nervous system are described. Activation of somatic or parasympathetic efferent nerves can produce contraction of striated or smooth muscle in the bladder, rectum, and sphincters. Activation of afferent nerves can produce reflex activation of somatic muscle and reflex inhibition or activation of smooth muscle in these organs. In clinical practice these techniques have been used to produce effective emptying of the bladder and bowel in patients with spinal cord injury and to improve continence of urine and feces. Stimulation of parasympathetic efferents can produce sustained erection of the penis, and stimulation of the nerves to the seminal vesicles can produce seminal emission. Reflex erection and ejaculation can also be produced by stimulation of afferent nerves. Experimental techniques for controlling emptying and continence by a single device, and prospects for comprehensive control of bladder, bowel, and sexual function by electrical techniques are described. These may include more selective electrodes, inactivation of nerves by specific stimulus parameters, greater use of sensors, and networking of implanted components connected to the central and peripheral nervous system.


Subject(s)
Electric Stimulation Therapy/methods , Gastrointestinal Diseases/therapy , Sexual Dysfunction, Physiological/therapy , Urinary Bladder Diseases/therapy , Gastrointestinal Diseases/etiology , Humans , Peripheral Nerves/physiology , Sexual Dysfunction, Physiological/etiology , Spinal Cord Injuries/complications , Spinal Cord Injuries/therapy , Urinary Bladder Diseases/etiology
13.
Eur J Neurosci ; 34(11): 1839-46, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22082003

ABSTRACT

Functional imaging studies, using blood oxygen level-dependent signals, have demonstrated cortical reorganization of forearm muscle maps towards the denervated leg area following spinal cord injury (SCI). The extent of cortical reorganization was predicted by spinal atrophy. We therefore expected to see a similar shift in the motor output of corticospinal projections of the forearm towards more denervated lower body parts in volunteers with cervical injury. Therefore, we used magnetic resonance imaging-navigated transcranial magnetic stimulation (TMS) to non-invasively measure changes in cortical map reorganization of a forearm muscle in the primary motor cortex (M1) following human SCI. We recruited volunteers with chronic cervical injuries resulting in bilateral upper and lower motor impairment and severe cervical atrophy and healthy control participants. All participants underwent a T1-weighted anatomical scan prior to the TMS experiment. The motor thresholds of the extensor digitorum communis muscle (EDC) were defined, and its cortical muscle representation was mapped. The centre of gravity (CoG), the cortical silent period (CSP) and active motor thresholds (AMTs) were measured. Regression analysis was used to investigate relationships between trauma-related anatomical changes and TMS parameters. SCI participants had increased AMTs (P = 0.01) and increased CSP duration (P = 0.01). The CoG of the EDC motor-evoked potential map was located more posteriorly towards the anatomical hand representation of M1 in SCI participants than in controls (P = 0.03). Crucially, cord atrophy was negatively associated with AMT and CSP duration (r(2) ≥ 0.26, P < 0.05). In conclusion, greater spinal cord atrophy predicts changes at the cortical level that lead to reduced excitability and increased inhibition. Therefore, cortical forearm motor representations may reorganize towards the intrinsic hand motor representation to maximize output to muscles of the impaired forearm following SCI.


Subject(s)
Cerebral Cortex/anatomy & histology , Cerebral Cortex/physiology , Cervical Vertebrae , Forearm/anatomy & histology , Forearm/physiology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Adult , Atrophy/pathology , Atrophy/physiopathology , Brain Mapping/methods , Evoked Potentials, Motor/physiology , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Muscle, Skeletal/innervation , Muscle, Skeletal/physiopathology , Perception/physiology , Transcranial Magnetic Stimulation
14.
Brain ; 134(Pt 6): 1610-22, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21586596

ABSTRACT

The impact of traumatic spinal cord injury on structural integrity, cortical reorganization and ensuing disability is variable and may depend on a dynamic interaction between the severity of local damage and the capacity of the brain for plastic reorganization. We investigated trauma-induced anatomical changes in the spinal cord and brain, and explored their relationship to functional changes in sensorimotor cortex. Structural changes were assessed using cross-sectional cord area, voxel-based morphometry and voxel-based cortical thickness of T1-weighted images in 10 subjects with cervical spinal cord injury and 16 controls. Cortical activation in response to right-sided (i) handgrip; and (ii) median and tibial nerve stimulation were assessed using functional magnetic resonance imaging. Regression analyses explored associations between cord area, grey and white matter volume, cortical activations and thickness, and disability. Subjects with spinal cord injury had impaired upper and lower limb function bilaterally, a 30% reduced cord area, smaller white matter volume in the pyramids and left cerebellar peduncle, and smaller grey matter volume and cortical thinning in the leg area of the primary motor and sensory cortex compared with controls. Functional magnetic resonance imaging revealed increased activation in the left primary motor cortex leg area during handgrip and the left primary sensory cortex face area during median nerve stimulation in subjects with spinal cord injury compared with controls, but no increased activation following tibial nerve stimulation. A smaller cervical cord area was associated with impaired upper limb function and increased activations with handgrip and median nerve stimulation, but reduced activations with tibial nerve stimulation. Increased sensory deficits were associated with increased activations in the left primary sensory cortex face area due to median nerve stimulation. In conclusion, spinal cord injury leads to cord atrophy, cortical atrophy of primary motor and sensory cortex, and cortical reorganization of the sensorimotor system. The degree of cortical reorganization is predicted by spinal atrophy and is associated with significant disability.


Subject(s)
Cerebral Cortex/physiopathology , Disabled Persons , Recovery of Function/physiology , Spinal Cord Injuries/complications , Spinal Cord Injuries/pathology , Adult , Aged , Analysis of Variance , Atrophy/pathology , Brain Mapping , Cerebral Cortex/blood supply , Disability Evaluation , Electric Stimulation/methods , Humans , Imaging, Three-Dimensional/methods , Magnetic Resonance Imaging/methods , Male , Median Nerve/physiology , Middle Aged , Regression Analysis , Spinal Cord/blood supply , Spinal Cord/pathology , Statistics, Nonparametric , Tibial Nerve/physiology , Upper Extremity/physiopathology , Wrist/innervation
15.
NeuroRehabilitation ; 24(3): 237-42, 2009.
Article in English | MEDLINE | ID: mdl-19458431

ABSTRACT

INTRODUCTION: Upright posture confers numerous medical and social benefits to a spinal cord injured (SCI) patient. Doing so is limited by symptoms of orthostatic hypotension. This is a common secondary impairment among tetraplegic sufferers. OBJECTIVE: Establish the proportion of SCI patients who are restricted from using standing apparatus, such as standing frames and standing wheelchairs, because of inducing symptomatic orthostatic hypotension or the fear of developing these disabling symptoms. STUDY DESIGN: Survey conducted by Internet-accessible electronic questionnaire. Questionnaire validated for reliability and accuracy. RESULTS: 293 respondents. Mean age 44.6; 76% male. Median time from injury: 7 years. 38% suffered with orthostatic hypotension; majority were complete injuries and all (except one - T12) were T5 or above level. 52% replied that they were using standing wheelchairs or frames. Of these, 59 (20% of total) stated that orthostatic hypotension symptoms were limiting the use of their upright apparatus. Of those who did not use standing wheelchairs or frames, 16 (5.5% of total) reported that this was because of the fear of worsening their orthostatic hypotension. CONCLUSION: Orthostatic hypotension restricts standing apparatus use in a large proportion (a total of 25.5% of respondents in this survey) of SCI patients.


Subject(s)
Hypotension, Orthostatic/etiology , Orthopedic Equipment/statistics & numerical data , Patient Compliance , Spinal Cord Injuries/complications , Spinal Cord Injuries/rehabilitation , Adult , Fear , Female , Health Surveys , Humans , Hypotension, Orthostatic/psychology , Hypotension, Orthostatic/rehabilitation , Internet , Male , Posture/physiology , Spinal Cord Injuries/psychology , Wheelchairs/statistics & numerical data
16.
Anal Chem ; 81(1): 288-95, 2009 Jan 01.
Article in English | MEDLINE | ID: mdl-19117456

ABSTRACT

Human seminal fluid (HSF) is a complex mixture of reacting glandular metabolite and protein secretions that provides critical support functions in fertilization. We have employed 600-MHz (1)H NMR spectroscopy to compare and contrast the temporal biochemical and biophysical changes in HSF from infertile men with spinal cord injury compared to age-matched controls. We have developed new approaches to data analysis and visualization to facilitate the interpretation of the results, including the first application of the recently published K-STOCSY concept to a biofluid, enhancing the extraction of information on biochemically related metabolites and assignment of resonances from the major seminal protein, semenogelin. Principal components analysis was also applied to evaluate the extent to which macromolecules influence the overall variation in the metabolic data set. The K-STOCSY concept was utilized further to determine the relationships between reaction rates and metabolite levels, revealing that choline, N-acetylglucosamine, and uridine are associated with higher peptidase activity. The novel approach adopted here has the potential to capture dynamic information in any complex mixture of reacting chemicals including other biofluids or cell extracts.


Subject(s)
Infertility, Male/metabolism , Nuclear Magnetic Resonance, Biomolecular/methods , Semen/metabolism , Spinal Cord Injuries/metabolism , Acetylglucosamine/metabolism , Biophysical Phenomena , Case-Control Studies , Choline/metabolism , Female , Humans , Infertility, Male/etiology , Male , Peptide Hydrolases/metabolism , Principal Component Analysis , Protons , Semen/chemistry , Spinal Cord Injuries/complications , Uridine/metabolism
17.
Clin Chem ; 54(12): 2063-6, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18832471

ABSTRACT

BACKGROUND: Compromised sexual health is a major rehabilitative barrier for men with lower-spinal cord injury (SCI). Although studies have revealed decreased sperm motility, the quantitative biochemical changes that underlie the infertility mechanism remain poorly understood. METHODS: We employed a nontargeted approach combining 800 MHz hydrogen nuclear magnetic resonance ((1)H NMR) spectroscopy and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) with pattern recognition methods to analyze seminal fluid metabolite profiles in 10 men with and 8 without SCI above thoracic vertebra 10 (T10). RESULTS: The metabolic phenotype for SCI could be predicted from the (1)H NMR data. The median concentration of uridine in fertile controls was 1.55 mmol/L (range 1.0-5.0 mmol/L), but was undetectable by both NMR and MS in all but 2 individuals from the SCI group, one who later fathered a child without assisted fertility techniques. CONCLUSIONS: We hypothesize that uridine is likely to be an essential precursor to metabolites required for capacitation and is a potential marker for the prognosis of post-SCI functional fertility recovery. We derived the term "seminal oligouridinosis" to describe this newly identified condition.


Subject(s)
Infertility, Male/diagnosis , Semen/chemistry , Spinal Cord Injuries/complications , Uridine/analysis , Biomarkers/analysis , Chromatography, Liquid , Humans , Infertility, Male/etiology , Magnetic Resonance Spectroscopy , Male , Mass Spectrometry , Semen/metabolism , Uridine/metabolism
18.
J Spinal Cord Med ; 31(1): 27-32, 2008.
Article in English | MEDLINE | ID: mdl-18533408

ABSTRACT

OBJECTIVE/BACKGROUND: Neurogenic reproductive dysfunction in men with spinal cord injury (SCI) is common and the result of a combination of impotence, ejaculatory failure, and abnormal semen characteristics. It is well established that the semen quality of men with SCI is poor and that changes are seen as early as 2 weeks after injury. The distinguishing characters of poor quality are abnormal sperm motility and viability. In the majority of the men with SCI, the sperm count is not abnormal. We elaborate on the effects of the SCI on semen parameters that may contribute to poor motility and poor viability. METHODS: Review. DESIGN: PubMed and MEDLINE databases were searched using the following key words: spinal cord injuries, fertility, sexual dysfunction, and spermatogenesis. All literature was reviewed by the team of authors according to the various stages of sperm development and transport in the male reproductive cycle. FINDINGS: The cause of asthenozoospermia appears to be multifactorial. CONCLUSION: Current literature does not support the preeminence of a single factor relating to neurogenic reproductive dysfunction in men with SCI. After SCI, there is ample evidence of disturbance of sperm production, maturation and storage, and transport due to an abnormal neuroendocrine milieu. Semen quality seems to be primarily affected by changes to the seminal plasma constituents, type of bladder management, and the neurogenic impairment to the ejaculatory function. Further focused and structured studies are required.


Subject(s)
Semen/physiology , Sexual Dysfunction, Physiological/etiology , Spinal Cord Injuries/complications , Animals , Asthenozoospermia/etiology , Humans , Male , PubMed/statistics & numerical data
19.
J Rehabil Res Dev ; 43(4): 553-64, 2006.
Article in English | MEDLINE | ID: mdl-17123193

ABSTRACT

Noninvasive functional magnetic stimulation (FMS) of the sacral nerve roots can activate gluteal muscles. We propose the use of sacral anterior root stimulator (SARS) implants to prevent ischial pressure ulcers in the spinal cord injury (SCI) population. In this study, we (1) investigated the acute effects of sacral FMS on ischial pressure, skin blood content, and oxygenation changes in people with SCI and demonstrated the utility of FMS as an assessment tool, and (2) showed that similar effects are possible with electrical stimulation via a SARS implant. Results indicated that sacral nerve root stimulation, either by FMS or implanted electrical stimulation, induced sufficient gluteus maximus contraction to significantly change subjects' ischial pressures and cutaneous hemoglobin and oxygenation during sitting. In addition to these beneficial acute effects, chronic stimulation via a SARS implant may build gluteal muscle bulk and prevent or reduce pressure ulcers in the SCI population.


Subject(s)
Electric Stimulation Therapy , Oxygen/metabolism , Pressure Ulcer/etiology , Pressure Ulcer/prevention & control , Spinal Cord Injuries/complications , Spinal Cord Injuries/metabolism , Adolescent , Adult , Aged , Buttocks , Electric Stimulation Therapy/methods , Hemoglobins/metabolism , Humans , Magnetics/therapeutic use , Middle Aged , Skin/metabolism , Spinal Nerve Roots
20.
J Rehabil Res Dev ; 43(2): 209-18, 2006.
Article in English | MEDLINE | ID: mdl-16847787

ABSTRACT

Neuromuscular stimulation via the sacral nerve roots is proposed for prevention of ischial pressure ulcers following a spinal cord injury (SCI). Acute effects of sacral functional magnetic stimulation (FMS) on seat interface pressure changes were investigated in five nondisabled volunteers. Similar effects were demonstrated with functional electrical stimulation in people with SCI who used a sacral anterior root stimulator implant. The results indicated that sacral nerve root stimulation, either by FMS or implanted electrical stimulation, induced gluteus maximus contraction and mild pelvic tilt sufficient for clinically significant reductions in ischial pressures during sitting.


Subject(s)
Electric Stimulation Therapy/methods , Lumbosacral Plexus/physiopathology , Pressure Ulcer/prevention & control , Spinal Cord Injuries/rehabilitation , Adult , Cohort Studies , Female , Follow-Up Studies , Humans , Ischium/physiopathology , Male , Middle Aged , Pressure , Pressure Ulcer/etiology , Probability , Risk Assessment , Spinal Cord Injuries/complications , Spinal Nerve Roots/physiopathology , Treatment Outcome
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