The brain and behavioral correlates of motor-related analgesia (MRA).

The human motor system has the capacity to act as an internal form of analgesia. Since the discovery of the potential influence of motor systems on analgesia in rodent models, clinical applications of targeting the motor system for analgesia have been implemented. However, a neurobiological basis for motor activation's effects on analgesia is not well defined. Motor-related analgesia (MRA) is a phenomenon wherein a decrease in pain symptoms can be achieved through either indirect or direct activation of the motor axis. To date, research has focused on (a) evaluating the pain-motor interaction as one focused on the acute protection from painful stimuli; (b) motor cortex stimulation for chronic pain; or (c) exercise as a method of improving chronic pain in animal and human models. This review evaluates (1) current knowledge surrounding how pain interferes with canonical neurological performance throughout the motor axis; and (2) the physiological basis for motor-related analgesia as a means to reduce pain symptom loads for patients. A proposal for future research directions is provided.

Biological and behavioral markers of pain following nerve injury in humans.

The evolution of peripheral and central changes following a peripheral nerve injury imply the onset of afferent signals that affect the brain. Changes to inflammatory processes may contribute to peripheral and central alterations such as altered psychological state and are not well characterized in humans. We focused on four elements that change peripheral and central nervous systems following ankle injury in 24 adolescent patients and 12 age-sex matched controls. Findings include (a) Changes in tibial, fibular, and sciatic nerve divisions consistent with neurodegeneration; (b) Changes within the primary motor and somatosensory areas as well as higher order brain regions implicated in pain processing; (c) Increased expression of fear of pain and pain reporting; and (d) Significant changes in cytokine profiles relating to neuroinflammatory signaling pathways. Findings address how changes resulting from peripheral nerve injury may develop into chronic neuropathic pain through changes in the peripheral and central nervous system.

Neurophysiological assessment of lower-limb voluntary control in incomplete spinal cord injury.

STUDY DESIGN: Cross-sectional retrospective study of a neurophysiological method of voluntary motor control characterization. OBJECTIVES: This study was undertaken to validate the surface electromyography (sEMG)-based voluntary response index (VRI) as an objective, quantitative, laboratory measure of spinal cord injury severity in terms of voluntary motor control disruption. SETTING: VA Medical Centers in Houston and Dallas Texas, USA. METHODS: A total of 67 subjects with incomplete spinal cord injury (iSCI), American Spinal Injury Association Impairment Scale (AIS)-C (n = 32) and -D (n = 35) were studied. sEMG recorded during a standardized protocol including eight lower-limb voluntary motor tasks was analyzed using the VRI method that relates multi-muscle activation patterns of SCI persons to those of healthy-subject prototypes (n = 15). The VRI is composed of a measure of the amount of the sEMG activity (magnitude) and the distribution of activity across muscle groups compared to that of healthy subjects for each motor task (similarity index, SI). These resulting VRI components, normalized magnitude and SI, were compared to AIS clinical findings in this study. Receiver operating characteristic analysis was performed to determine the SI values best separating AIS-C and AIS-D subjects. RESULTS: Magnitude and SI for AIS-C subjects had mean values of 0.27 +/- 0.32 and 0.65 +/- 0.21, respectively. Both parameters were significantly larger in the AIS-D subjects (0.78 +/- 0.43 and 0.93 +/- 0.06), respectively (P < 0.01). An SI value of 0.85 was found to separate AIS-C and AIS-D groups with a sensitivity of 0.89 and a specificity of 0.81. Further, the VRI of each leg strongly correlated with the respective AIS motor score (0.80, r < 0.01). CONCLUSIONS: In the domains of voluntary motor control, the sEMG-based VRI demonstrated adequate face validity and sensitivity to injury severity as currently measured by the AIS. SPONSORSHIP: Veterans Affairs Medical Center.

Neurophysiological examination of the corticospinal system and voluntary motor control in motor-incomplete human spinal cord injury.

This study employed neurophysiological methods to relate the condition of the corticospinal system with the voluntary control of lower-limb muscles in persons with motor-incomplete spinal cord injury. It consisted of two phases. In a group of ten healthy subjects, single and paired transcranial magnetic stimulation (TMS) of the motor cortex was used to study the behavior of the resulting motor evoked potentials (MEP) in lower-limb muscles. Interstimulus intervals (ISIs) of 15-100 ms were examined for augmentation of test MEPs by threshold or subthreshold conditioning stimuli. The second phase of this study examined eight incomplete spinal cord injured (iSCI) subjects, American Spinal Injury Association Impairment Scale C (n = 5) and D (n = 3) in whom voluntary motor control was quantified using the surface EMG (sEMG) based Voluntary Response Index (VRI). The VRI is calculated to characterize relative output patterns across ten lower-limb muscles recorded during a standard protocol of elementary voluntary motor tasks. VRI components were calculated by comparing the distribution of sEMG in iSCI subjects with prototype patterns collected from 15 healthy subjects using the same rigidly administered protocol, The resulting similarity index (SI) and magnitude values provided the measure of voluntary motor control. Corticospinal system connections were characterized by the thresholds for MEPs in key muscles. Key muscles were those that function as the prime-movers, or agonists for the voluntary movements from which the VRI data were calculated. Results include healthy-subject data that showed significant increases in conditioned MEP responses with paired stimuli of 15-50 ms ISI. Stimulus pairs of 75 and 100 ms showed no increase in MEP peak amplitude over that of the single-pulse conditioning stimulus alone, usually no response. For the iSCI subjects, 42% of the agonists responded to single-pulse TMS and 25% required paired-pulse TMS to produce an MEP. American Spinal Injury Association Impairment Scale component motor scores for agonist muscles, Quadriceps, Tibialis Anterior, and Triceps Surae, were significantly lower where MEPs could not be obtained (p < 0.05). VRI values were also significantly lower for motor tasks with agonists that had no resting MEP (p < 0.01). Therefore, the presence of a demonstrable connection between the motor cortex and spinal motor neurons in persons with SCI was related to the quality of post-injury voluntary motor control as assessed by the VRI.

Assessment of mercury emissions inventories for the Great Lakes states.

Anthropogenic mercury (Hg) air emissions for the eight Great Lakes states in 1999-2000 were evaluated by analyzing three inventories. The US Environmental Protection Agency (EPA) National Emissions Inventory (NEI) had the most complete coverage for all states, and total Hg emissions ranged from 4226 lb in Minnesota to 15,828 lb in Pennsylvania. Coal-fired electric utilities accounted for 52.7% of the region's Hg emissions, varying from 20.2% of the total in New York to 67.5% in Ohio. Other important contributors to regional emissions included municipal waste combustion (5.6%), mercury-cell chlor-alkali plants and hazardous-waste incinerators (4% each), stationary internal combustion engines (ICEs) (3.5%), industrial, commercial, and institutional (ICI) boilers (3.3%), and lime manufacturing (3.0%). Although medical waste incineration accounted for just over 1% of regional emissions using the original classifications, the inclusion of health care facilities that may have been inappropriately identified with other sectors would increase the sector to 4.5% of regional emissions (and decrease the stationary ICE sector to 1.4% of the regional total). There were substantial differences for some sectors between the NEI and the Great Lakes Regional Air Toxics Emissions Inventory (GLEI), as well as unexplained differences within inventories between states (particularly for the cement, lime, and asphalt industries, and for lamp breakage). Toxics Release Inventory data for 2000 mainly covered electric utilities, and differences from the NEI were significant for several states. An independent assessment indicates the possibility of underestimated Hg emissions by about twofold for ICI boilers, although data for the sector (in particular concerning fuel oil emissions) are highly uncertain. Limited data indicate the likelihood of significant underestimates of electric arc furnace mercury emissions in the NEI and GLEI inventories. Several measures are here identified for improving the reliability of the inventories, both for modeling of atmospheric transport and deposition modeling and for tracking progress in Hg reduction initiatives.

Toward an objective interpretation of surface EMG patterns: a voluntary response index (VRI).

Individuals with incomplete spinal cord injuries (SCI) retain varying degrees of voluntary motor control. The complexity of the motor control system and the nature of the recording biophysics have inhibited efforts to develop objective measures of voluntary motor control. This paper proposes the definition and use of a voluntary response index (VRI) calculated from quantitative analysis of surface electromyographic (sEMG) data recorded during defined voluntary movement as a sensitive measure of voluntary motor control in such individuals. The VRI is comprised of two numeric values, one derived from the total muscle activity recorded for the voluntary motor task (magnitude), and the other from the sEMG distribution across the recorded muscles (similarity index (SI)). Calculated as a vector, the distribution of sEMG from the test subject is compared to the average vector calculated from sEMG recordings of the same motor task from 10 neurologically intact subjects in a protocol called brain motor control assessment (BMCA). To evaluate the stability of the VRI, a group of five healthy subjects were individually compared to the prototype, average healthy-subject vectors for all of the maneuvers. To evaluate the sensitivity of this method, the VRI was obtained from two SCI subjects participating in other research studies. One was undergoing supported treadmill ambulation training, and the other a controlled withdrawal of anti-spasticity medications. The supported treadmill training patient's VRI, calculated from pre- and post-training BMCA recordings, reflected the qualitative changes in sEMG patterns and functional improvement of motor control. The VRI of the patient followed by serial BMCA during medication withdrawal also reflected changes in the motor control as a result of changes in anti-spasticity medication. To validate this index for clinical use, serial studies using larger numbers of subjects with compromised motor control should be performed.

Is sexual intercourse a significant cause of haematuria?

OBJECTIVES: To determine whether recent sexual intercourse might be a cause of microscopic haematuria in patients referred to a urological unit following dipstick detection of urinary haemoglobin. SUBJECTS AND METHODS: Forty-eight volunteers (24 men and 24 women) consented to have heterosexual intercourse with their regular partner, and to provide samples of urine for testing before and from the first void on the morning after intercourse. After appropriate instruction, volunteers tested their own urine for the presence of blood using standard dipsticks. Any volunteer with haematuria either before or after intercourse was offered a standard haematuria assessment. The results were analysed using the chi-squared test. RESULTS: None of the volunteers tested positively for haematuria immediately before sexual intercourse; six of the 24 women (25%), but no men, became positive after intercourse (P < 0.01). Only one of the six women accepted the offer of a haematuria evaluation and no pathology was identified. CONCLUSION: These results suggest that up to a quarter of women develop microscopic haematuria as a direct result of sexual intercourse. A history of recent sexual intercourse should therefore be considered when assessing the clinical significance of microscopic haematuria in women.

Supported treadmill ambulation training after spinal cord injury: a pilot study.

OBJECTIVES: To conduct a pilot study of weight-supported ambulation training after incomplete spinal cord injury (SCI), and to assess its safety. DESIGN: Quasiexperimental, repeated measures, single group. SETTING: Veterans Affairs medical center. PATIENTS: Three subjects with incomplete, chronic, thoracic SCIs; 2 classified as D on the American Spinal Injury Association (ASIA) impairment scale and 1 as ASIA impairment scale C. INTERVENTION: Subjects participated in 12 weeks of training assisted by 2 physical therapists. The training consisted of walking on a treadmill while supported by a harness and a pneumatic suspension device. Support started at 40% of body weight and a treadmill speed of.16kmph, and progressed by reducing support and increasing treadmill speed and continuous treadmill walking time up to 20 minutes. Training was conducted for 1 hour per day, 5 days per week for 3 months. Treadmill walking occurred for 20 minutes during the sessions. MAIN OUTCOME MEASURES: Gait function (speed, endurance, walking status, use of assistive device and orthotics); oxygen costs of walking; brain motor control assessment; self-report indices; ASIA classification; muscle function test; and safety. RESULTS: All 3 subjects increased gait speed (.118m/s initially to.318m/s after training 12wk), and gait endurance (20.3m/5min initially to 63.5m/5min). The oxygen costs decreased from 1.96 to 1.33mL x kg(-1) x m(-1) after 12 weeks of training. CONCLUSIONS: This pilot study suggests that supported treadmill ambulation training can improve gait for individuals with incomplete SCIs by using objective gait measures. The self-report indices used have promise as patient-centered outcome measures of this new form of gait training. A larger, controlled study of this technique is warranted.

Equipment specifications for supported treadmill ambulation training.

Supported Treadmill Ambulation Training (STAT) is a mode of therapy for gait retraining for patients with spinal cord injuries or other upper motor neuron dysfunction. The STAT program involves simultaneously supporting a portion of the patient's weight while gait training on a treadmill. STAT has been successful in improving the gait of many research subjects, but has not been widely applied in clinical practice. The goal of this study was to acquire practical, clinically useful information regarding this therapeutic intervention in order to remove barriers to its use. This manuscript enumerates equipment specifications for the treadmill, body weight support (BWS) system, and harness. The ergonomics of the work space are also considered, since the therapist(s) will need access to the patient's legs during therapy. The specific recommendations were determined through prior clinical experience, consultation of anthropometric tables, and application of engineering principles. The guidelines listed are intended to facilitate safe and effective application of the therapy at minimum hardware cost.

Selective modifiers of glutathione biosynthesis and 'repriming' of vascular smooth muscle photorelaxation.

Photorelaxation of vascular smooth muscle (VSM) is caused by the release of nitric oxide (NO) from a finite molecular store that can be depleted by irradiating pre-contracted arteries with visible light. The ability of an 'exhausted' vessel to respond to a further period of illumination is lost temporarily but then recovers slowly as the photosensitive store is reconstituted in the dark. The recovery process, termed repriming, displays an absolute requirement for endothelium-derived NO and is inhibited by pre-treating arteries with ethacrynic acid, a thiol-alkylating agent. Here we demonstrate that agents that up- or down-regulate glutathione (GSH) biosynthesis influence the extent to which the store is regenerated in the dark. Isolated rat tail arteries (RTAs) were perfused internally with Krebs solution containing phenylephrine (PE; mean [PE] +/- s.e.mean: 5. 78+/-0.46 microM) and periodically exposed to laser light (lambda=514.5 nm, 6.3 mW cm(-2) for 6 min). Photorelaxations of control RTAs were compared with those from either (a) vessels taken from animals previously injected i.p. with buthionine sulphoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase (three injections, 100 mg kg(-1) at 8 h intervals); or (b) isolated RTAs that were perfused ex vivo with oxothiazolidine (OXO), a precursor of cysteine (10(-4) M OXO for 60 min). RTAs from BSO-treated animals exhibited attenuated photorelaxations: the mean (+/-s.e.mean) amplitude of the response recorded after 72 min recovery in the dark was 12.4+/-1.6% versus 21.4+/-2.9% for control arteries (n=5; P<0. 01). Conversely RTAs treated with OXO and allowed to recover for a similar period showed enhanced photorelaxations, 32.6+/-6.3% as compared to 21.4+/-2.9% for control arteries (n=5; P<0.01). A hyperbolic curve fit to repriming curves for BSO-treated and control arteries returned asymptote values (maximum photorelaxations) of (mean +/- s.e.mean) 24.2+/-3.2% and 55.2+/-8.5%, respectively. The level of GSH in RTA extracts was measured by high-pressure liquid chromatography (HPLC). Injecting animals with BSO decreased GSH to 85% of control levels (P<0.05) while treatment of isolated vessels with OXO resulted in a 31% increase above control levels (P<0.05). Thus, drug-induced changes in RTA GSH levels were positively correlated with altered photorelaxations. The results lead us to postulate that the photosensitive store in VSM is generated, at least in part, from intracellular GSH which becomes converted to S-nitrosoglutathione (GSNO) by nitrosating species that are formed ultimately from endothelium-derived NO. The possible physiological significance of a photolabile store of NO in VSM is discussed briefly.

Nonhomologous bioinjectable materials in urology: 'size matters'?

OBJECTIVE: To assess the factors that influence how particles might become fixed in tissues or migrate from them, by measuring the size of the injectable particles, their susceptibility to phagocytosis and their affinity for fibroblast attachment in culture. MATERIALS AND METHODS: The particle size of three types of particulate unphysiological bioinjectable material, i.e. Urocol (Genesis Medical, Ltd., London), Macroplastiquetrade mark (Uroplasty Ltd., Reading, UK) and Urethrin (Mentor Medical Systems, Wantage, UK) was analysed using phase-contrast light microscopy and confocal microscopy. Human monocytes from peripheral blood were incubated with the three materials in phagocytic studies, where ingestion was determined by confocal microscopy. A fibroblast cell line was used to ascertain the ability of the particles to act as a substrate for cell attachment in culture. RESULTS: The mean (SEM) maximum particle diameters of Macroplastique, Urethrin and Urocol were 209 (5.10) microm, 49 (1.52) microm and 14 (0.39) microm, respectively. Rat peritoneal macrophages and human peripheral blood monocytes commonly ingested Urocol particles; the phagocytosis of Urethrin was rare and that of Macroplastique was not detected. Fibroblasts adhered to Urocol paste and Urethrin particles, but not to Macroplastique. CONCLUSION: Published reports of particle size and phagocytosis are confusing, but a relationship clearly exists. Macroplastique is the largest particle and is least likely to be phagocytosed by human mononuclear phagocytes. Urocol paste is the slowest to dissipate in culture conditions; the flat surfaces of Urethrin, but not Macroplastique, can serve as a substrate for fibroblast anchorage.

A prospective study of the natural history of hematuria associated with benign prostatic hyperplasia and the effect of finasteride.

PURPOSE: We prospectively studied the effect of finasteride on chronic hematuria associated with benign prostatic hyperplasia. MATERIALS AND METHODS: We prospectively evaluated 57 patients with chronic intermittent hematuria who were randomized to a finasteride treated or a control arm. RESULTS: In the untreated control group hematuria recurred in 17 patients (63%) within a year but in only 4 (14%) in the finasteride group, which was a statistically significant difference (p <0.05). Surgery was required for bleeding in 7 controls (26%), while no patient on finasteride required surgery. CONCLUSIONS: Hematuria secondary to prostatic bleeding may be significant if not treated. Finasteride appears to be effective for suppressing hematuria caused by benign prostatic hyperplasia and should be considered as treatment.

The use of small intestine in bladder reconstruction.

Reconstruction of the bladder is a treatment available to patients who have a diseased or damaged bladder, and small bowel is the most commonly used tissue. Augmentation cystoplasty increases the total bladder capacity, whereas substitution cystoplasty replaces the whole organ. This is either drained through a continent cutaneous stoma or is reanastomosed to the urethra as an orthotopic reconstruction. Although the treatment for invasive bladder cancer has not changed greatly in the last few decades, the use of orthotopic bladder reconstruction allows for a great improvement in the quality of life for patients who undergo cystectomy. These reconstructive techniques can also be offered to patients with other forms of pelvic malignancy that involve the bladder.

Haematuria associated with BPH-Natural history and a new treatment option.

Bleeding of prostatic origin is usually caused by the friable hypervascularity of the prostate, the vessels of which are easily disrupted by physical activity. The condition is often ignored after the patient has been fully investigated and more serious causes for bleeding excluded and treatment is often withheld unless the bleeding becomes excessive. We analysed the clinical effect of finasteride in the treatment of this condition. We retrospectively reviewed 42 patients diagnosed as having haematuria secondary to bleeding from a benign prostate. Eighteen patients were simply reassured and given no treatment. Twenty-four patients with prostatic bleeding were treated using finasteride. All case notes were reviewed and the patients were contacted by telephone. Of 18 patients who had prostatic bleeding but did not receive treatment the mean age was 70 y and the mean follow-up was 10 months; two had died, nine had no further bleeding, two had a single episode of bleeding requiring no treatment, six had several bleeding episodes of whom one started finasteride, one refused treatment, and three required TURP. In the group treated with finasteride the mean follow up was 9 months, the mean age of the patients was 75 y. Twenty patients had no further bleeding, one patient experienced minor intermittent bleed and required no further treatment. Two patients died of non-urological causes, one patient stopped the treatment because of impotence and one patient had mild gynecomastia. Haematuria secondary to prostatic bleeding can be significant if not treated. Finasteride appears to be effective in suppressing haematuria caused by benign prostatic hyperplasia and should be considered in treating this problem.