Treadmill measures of ambulation rates in ovine models of spinal cord injury and neuropathic pain.

Our laboratories are developing treadmill-based gait analysis employing sheep to investigate potential efficacy of intra-dural spinal cord stimulation in the treatment of spinal cord injury and neuropathic pain. As part of efforts to establish the performance characteristics of the experimental arrangement, this study measured the treadmill speed via a tachometer, video belt-marker timing and ambulation-rate observations of the sheep. The data reveal a 0.1-0.3% residual drift in the baseline (unloaded) treadmill speed which increases with loading, but all three approaches agree on final speed to within 1.7%, at belt speeds of ≈ 4 km/h. Using the tachometer as the standard, the estimated upper limit on uncertainty in the video belt-marker approach is ± 0.18 km h(-1) and the measured uncertainty is ± 0.15 km h(-1). Employment of the latter method in determining timing differences between contralateral hoof strikes by the sheep suggests its utility in assessing severity of SCI and responses to therapeutic interventions.

Biomechanical performance of an ovine model of intradural spinal cord stimulation.

The authors are developing a novel type of spinal cord stimulator, designed to be placed directly on the pial surface of the spinal cord, for more selective activation of target tissues within the dorsal columns. For pre-clinical testing of the device components, an ovine model has been implemented which utilizes the agility and flexibility of a sheep's cervical and upper thoracic regions, thus providing an optimal environment of accelerated stress-cycling on small gauge lead wires implanted along the dorsal spinal columns. The results are presented of representative biomechanical measurements of the angles of rotation and the angular velocities and accelerations associated with the relevant head, neck and upper back motions, and these findings are interpreted in terms of their impact on assessing the robustness of the stimulator implant systems.

MR-based measurement of spinal cord motion during flexion of the spine: implications for intradural spinal cord stimulator systems.

This study develops a means of delivering electrical stimuli directly to the pial surface of the spinal cord for treatment of intractable pain. This intradural implant must remain in direct contact with the cord as it moves within the spinal canal. Therefore, magnetic resonance imaging was used to measure the movement of the spinal cord between neutral and flexed-back positions in a series of volunteers (n = 16). Following flexion of the back, the mean change in the pedicle-to-spinal cord dorsal root entry zone distance at the T10-11 level was (8.5 ± 6.0) mm, i.e. a 71% variation in the range of rostral-caudal movement of the spinal cord across all patients. There will be a large spectrum of spinal cord strains associated with this observed range of rostral-caudal motions, thus calling for suitable axial compliance within the electrode bearing portion of the intradural implant.

Apparatus for simulating dynamic interactions between the spinal cord and soft-coupled intradural implants.

We have designed, built, and tested an apparatus used for investigating the biomechanical response of a novel intradural spinal cord stimulator to the simulated physiological movement of the spinal cord within the thecal sac. In this apparatus, the rostral-caudal displacements of an anthropomorphic spinal cord surrogate can be controlled with a resolution of approximately 0.1% of a target value for up to 10(7) lateral movement cycles occurring at a repetition rate of 2 Hz. Using this system, we have been able to determine that the restoring force of the stimulator's suspension system works in concert with the frictional coupling between the electrode array and the surrogate to overcome the 0.42 µN inertial force associated with the lateral motion of the array. The result is a positional stability of the array on the surrogate (in air) of better than 0.2 mm over ~500,000 movement cycles. Design modifications that might lead to improved physiological performance are discussed.

Applier tool for intradural spinal cord implants.

We have designed, built and tested a novel device for placing intradural neurmodulator implants directly on the pial surface of the spinal cord. This applier tool is designed for ergonomic handling of delicate electro-mechanical devices such as the Iowa-Patch™ spinal cord stimulator implant, which is aimed at overcoming certain shortcomings in the performance of standard epidural stimulator devices. The applier is approximately 14 cm long, 6 mm in diameter, made of stainless steel components, and has simple and reliable mechanisms for the attachment and release of the implant from it. We describe the design of the device, details of its construction, and its performance during in vivo testing of somatosensory evoked potentials in an ovine model of intradural spinal cord stimulation.

Isolation of coliphages specific to enterotoxigenic E. coli (ETEC).

Bacteriophages specific to Enterotoxigenic E. coli (ETEC) are reported for the first time. Out of 15 isolated phages only 10 were specific to strains of ETEC. All ten phages of dsDNA could be grouped into three different genotypes based on their RAPD patterns observed and it is likellly that they belong to only 3 different strains. The three phages yielded clear plaques on 10 strains of ETEC within 4-6 h at 37 degrees C.

Acceptability trials with ready to eat foods in a rural area.

Acceptability trials with three types of recipes was carried out on 184 young preschoolers (6 months to 35 months) residing in four nearby villages around Hyderabad. Results of this study indicated that among the 3 types of supplementary foods (Sweet Ready Mix, Sweet Ready Mix with Amylase and Therapeutic food tested here, the Therapeutic food was more acceptable (taste, smell and bulk) to the children. The criteria for acceptability of the food was defined as the ability of 75% of the children to consume 75% or more of the food supplement at one sitting for 70% of the days of the trial. The Therapeutic food, a calorie dense supplement, met the above criteria. The acceptability was poor for the Sweet Ready Mix and Sweet Ready Mix with Amylase (< 4%) mainly due to quantity rather than taste and smell as revealed by the mothers. The mothers of the children also liked the taste and smell of the therapeutic food better. Consumption of the therapeutic food caused minimal side effects like diarrhea and vomiting when compared to side effects after eating Sweet Ready Mix and Sweet Ready Mix with Amylase in children.

Iron fortified salt distribution through integrated child development services in Orissa - an assessment.

The present study was undertaken in two backward districts namely Phulbani and Sundargarh, of Orissa State, India, to study operational aspects of the distribution programme of iron fortified salt (IFS), and the extent of any overlap with the ongoing National Nutritional Anaemia Control Programme (NNACP) and possible toxic effects thereof. All IFS samples tested showed iron levels in the range of 800-1000 mg of elemental iron per I kg of iron fortified salt. Distribution of IFS to households was irregular and only 40% of the households had stocks of IFS at the time of home visits. None of the households using IFS reported any kind of adverse effects. Prevalence of anaemia (blood haemoglobin level of less than 11 g/dl) was highest among pregnant women (90.9%) followed by lactating women (88.7%), school aged children (84.4%) and preschool children (77.9%) respectively. Folifer tablets are being distributed to pregnant, lactating women and preschool children. Adult tablets contain 60 mg of elemental iron in the form of ferrous sulphate (FeSO4) and 500 m g of folic acid. Tablets distributed to children contain 20 mg of elemental iron and 100 m g of folic acid. Enquires regarding distribution of folifer tablets showed that 71% of pregnant women, 22% of lactating women and 22% of children received the folifer tablets at sometime or other and no toxic effects were reported. These results indicate the necessity for some modifications in existing strategies for distribution of IFS in order that it be effective in the prevention of widespread anaemia.

Toxicity assessment of papaverine hydrochloride and papaverine-derived metabolites in primary cultures of rat hepatocytes.

The present study was undertaken to assess and compare the toxic effects of papaverine hydrochloride and its metabolites. Primary cell cultures of rat hepatocytes were treated with papaverine (papaver), 3'-O-desmethyl (3'-OH), 4'-O-desmethyl (4'-OH), and 6-O-desmethyl (6-OH) papaverine at 1 x 10(-5), 1 x 10(-4), and 1 x 10(-3) M for 4, 8, 12, and 24-h periods. Cell injury was determined by: a) cell viability using the trypan blue exclusion test; b) cytosolic enzyme leakage of lactate dehydrogenase and aspartate aminotransferase; c) morphologic alterations; and d) lactate:pyruvate (L:P) ratios. Cell cultures showed concentration- and time-dependent toxic responses. For example, a decrease in cell viability and an increase in enzyme leakage were observed after cell treatment with 1 x 10(-4) and 1 x 10(-3) M papaver for 8 h; 1 x 10(-3) M 6-OH papaverine for 8 h and 1 x 10(-4) M for 24 h; and 1 x 10(-3) M 4'-OH papaverine for 24 h (P less than 0.05). Furthermore, changes in morphology correlated to cell viability and enzyme release in those cultures treated with papaver, 4'-OH and 6-OH papaverine. Some of these changes included size deformation, cell detachment from the dishes, and cell necrosis. On the other hand, an increase in L:P ratios (P less than 0.05) was detected with papaver as early as 8 h with 1 x 10(-4) and 1 x 10(-3) M and 12 h with 1 x 10(-5) M; 6-OH showed an increase in L:P ratios at 8 h with 1 x 10(-3) M and 12 h with 1 x 10(-4) M; these changes were evident with with 4'-OH at 12 h with 1 x 10(-3) M. In contrast, cells treated with 3'-OH papaverine did not show significant damage with any time period and concentration used in this study. The results of this study indicate that papaverine-derived metabolites are less cytotoxic than its parent compound, papaver. The toxicity was ranked as follows: papaver greater than 6-OH greater than 4'-OH greater than -3'-OH.