Tetrahydrobiopterin in the prevention of hypertonia in hypoxic fetal brain.

OBJECTIVE: Tetrahydrobiopterin (BH(4)) deficiency is a cause of dystonia at birth. We hypothesized that BH(4) is a developmental factor determining vulnerability of the immature fetal brain to hypoxic-ischemic injury and subsequent motor deficits in newborns. METHODS: Pregnant rabbits were subjected to 40-minute uterine ischemia, and fetal brains were investigated for global and focal changes in BH(4). Newborn kits were assessed by neurobehavioral tests following vehicle and sepiapterin (BH(4) analog) treatment of dams. RESULTS: Naive fetal brains at 70% gestation (E22) were severely deficient for BH(4) compared with maternal and other fetal tissues. BH(4) concentration rapidly increased normally in the perinatal period, with the highest concentrations found in the thalamus compared with basal ganglia, frontal, occipital, hippocampus, and parietal cortex. Global sustained 40-minute hypoxia-ischemia depleted BH(4) in E22 thalamus and to a lesser extent in basal ganglia, but not in the frontal, occipital, and parietal regions. Maternal supplementation prior to hypoxia-ischemia with sepiapterin increased BH(4) in all brain regions and especially in the thalamus, but did not increase the intermediary metabolite, 7,8-BH(2). Sepiapterin treatment also reduced incidence of severe motor deficits and perinatal death following E22 hypoxia-ischemia. INTERPRETATION: We conclude that early developmental BH(4) deficiency plays a critical role in hypoxic-ischemic brain injury. Increasing brain BH(4) via maternal supplementation may be an effective strategy in preventing motor deficits from antenatal hypoxia-ischemia.

Effect of tone-inhibiting casts and orthoses on gait. A case report.

In the adult case presented, inhibitory casting proved successful in decreasing the positive support reaction. When casting was discontinued, the positive reaction returned. To provide a long-term solution for this problem, a polypropylene tone-inhibiting AFO was fabricated. It incorporated the same principles as the casts. The success achieved with casting was rapidly regained and then surpassed with the use of the tone-inhibiting AFO. Natural recovery might be cited by some as the cause for improvement in the patient presented. However, the loss of improvement during the interval between the removal of the inhibitory casts and the initiation of the use of the tone-inhibiting AFO demonstrates that the casting and the position provided by the casts had a positive effect on our patient. This notion is further supported by the fact that our patient still required use of the tone-inhibiting AFO as late as March 1980. We have no explanation for the rapid improvement following the cranioplasty. Suggestions for further research would include a similar study with a larger number of subjects and the use of cinematography and kinesiological EMG during walking with and without tone-inhibiting casts and orthoses to determine the effect of the devices on spastic muscle groups and gait patterns.

The effects of tone-reducing orthotics on walking of an individual after incomplete spinal cord injury.

PURPOSE: Most literature about the efficacy of tone-reducing orthotics pertains to adults and children with central nervous system (CNS) pathology. There is relatively little mention of using this type of orthotic with adults after spinal cord injury (SCI). Therefore, the purpose of this study was to investigate whether tone-reducing orthotics have an effect on gait including electromyographic (EMG) activity, velocity, step length, time in double-limb support, and SCI-Functional Ambulation Inventory (SCI-FAI) scores for an individual with incomplete SCI and spasticity. METHODS: We used a single case design. The subject was a 25-year-old white male who was 16 months post-injury with a diagnosis of T6 left/T9 right sensory, L3 motor American Spinal Injury Association C incomplete SCI. Five different walking conditions were tested during each of two separate sessions: barefoot, shoes, foot plates, one ankle-foot orthosis (AFO) with a joint, and one with a tone-reducing AFO, and tone-reducing AFOs bilaterally. Surface EMG was used to record electrical activity of four muscle groups bilaterally. Step length, gait velocity, and time in double limb support were calculated for all five walking conditions. Gait parameters were further analyzed with video analysis using the SCI-FAI. RESULTS: Mean EMG was relatively constant in all muscle groups under all walking conditions with the exception of the gastrocnemius. In this muscle group, EMG activity with the use of tone-reducing orthotics was better modulated than the other conditions. Gait velocity and step length both increased with tone-reducing orthotics, whereas double limb support time decreased, thus improving the corresponding SCI-FAI score accordingly. CONCLUSION: The subject showed improvement in the control of his lower extremities while wearing bilateral tone-reducing AFOs as evidenced by an increased step length and gait velocity and a decrease in the amount of time spent in double limb support. Electromyographic data were less conclusive, although activity in the left gastrocnemius muscle group was more erratic under alternative walking conditions when compared to the tone-reducing AFOs.

Creatine as a compatible osmolyte in muscle cells exposed to hypertonic stress.

Exposure of C2C12 muscle cells to hypertonic stress induced an increase in cell content of creatine transporter mRNA and of creatine transport activity, which peaked after about 24 h incubation at 0.45 osmol (kg H(2)O)(-1). This induction of transport activity was prevented by addition of either cycloheximide, to inhibit protein synthesis, or of actinomycin D, to inhibit RNA synthesis. Creatine uptake by these cells is largely Na(+) dependent and kinetic analysis revealed that its increase under hypertonic conditions resulted from an increase in V(max) of the Na(+)-dependent component, with no significant change in the K(m) value of about 75 mumol l(-1). Quantitative real-time PCR revealed a more than threefold increase in the expression of creatine transporter mRNA in cells exposed to hypertonicity. Creatine supplementation significantly enhanced survival of C2C12 cells incubated under hypertonic conditions and its effect was similar to that obtained with the well known compatible osmolytes, betaine, taurine and myo-inositol. This effect seemed not to be linked to the energy status of the C2C12 cells because hypertonic incubation caused a decrease in their ATP content, with or without the addition of creatine at 20 mmol l(-1) to the medium. This induction of creatine transport activity by hypertonicity is not confined to muscle cells: a similar induction was shown in porcine endothelial cells.

A hard hand-positioning device to decrease wrist and finger hypertonicity: a sensorimotor approach for the patient with nonprogressive brain damage.

To investigate whether a hand-positioning device placed in the palm of a patient with nonprogressive brain damage will decrease hypertonicity of the flexor muscles of the hand through proprioreceptive sensory input to the alpha-gamma coactivation loop, a hard cone was placed in the affected hand of 11 subjects who had sustained cerebrovascular accidents and had flexor hypertonicity of the upper extremity. Measurements of hypertonicity and functionality were made weekly for four weeks. All subjects experienced a significant decrease in flexor hypertonicity. Only slight changes were observed in functionality.

Comparison of pharyngoesophageal segment pressure in total laryngectomy patients with and without pharyngeal neurectomy.

BACKGROUND: To compare pharyngoesophageal segment (PES) pressure values in total laryngectomy patients with and without pharyngeal neurectomy (PN) in the early postoperative period. METHODS: Forty-five previously untreated laryngeal carcinoma patients were enrolled into this prospective randomized study. Twenty of them underwent total laryngectomy with PN, and 25 underwent total laryngectomy without PN. PES pressures were measured on the tenth postoperative day with a four-channel catheter. RESULTS: Average PES pressures in patients with and without pharyngeal neurectomy were 12.82 +/- 6.11 mmHg and 17.40 +/-.72 mmHg respectively (p <.05). When compared with the critical point of 20 mmHg that is closely related to voice attainment in the group without pharyngeal neurectomy, 10 (40%) patients had pressure levels greater than 20 mmHg and in the other group only 1 (5%) patient had a pressure level greater than 20 mmHg. The difference between the groups with pressure levels greater than 20 mmHg was found to be statistically significant (p <.05). CONCLUSIONS: Pharyngeal neurectomy results in a statistically significant decrease of PES pressures in total laryngectomy patients.

Intramuscular ketamine, midazolam, and glycopyrrolate for pediatric sedation in the emergency department.

PURPOSE: The safety and efficacy of a new sedation technique for children with facial injuries in the emergency department were prospectively evaluated. MATERIALS AND METHODS: Thirty-seven children between the ages of 12 months and 7 years old who required sedation for minor surgical procedures were administered an intramuscular injection of ketamine (3 mg/kg), midazolam (0.05 mg/kg), and glycopyrrolate (0.005 mg/kg). A second 1-mg/kg intramuscular injection of ketamine alone was given if needed. Pulse rate, cardiac rhythm, respiratory rate, oxygen saturation, side effects, and behavior were recorded. RESULTS: Satisfactory sedation was achieved after a single injection in 32 children; five others required a second ketamine injection (1 mg/kg). Onset of anesthesia occurred within 6 minutes in 73% of the children who received one injection, and there were generally adequate working conditions for 30 minutes. The average time from initial injection to discharge was 76 minutes. Results of physiologic monitoring, behavioral ratings, and side effects are reported. Emergence delirium and hallucinations were not observed. Ketamine reliably produced dissociative anesthesia without loss of respiratory drive or protective airway tone. Midazolam reduced the incidence of ketamine-induced dysphoric reactions and muscular hypertonicity. CONCLUSION: The use of intramuscular ketamine, midazolam, and glycoyrrolate is a safe, effective, and practical approach to managing selected pediatric injuries in the emergency department. Advanced airway management proficiency is recommended for use of this technique.