Effects of intense noise exposure on fetal sheep auditory brain stem response and inner ear histology

OBJECTIVE: To evaluate, in two separate experiments, the effects of intense noise exposures delivered to fetal sheep in utero during a time of rapid auditory development. DESIGN: In the first experiment, auditory brain stem response (ABR) thresholds to clicks and tone bursts were recorded from chronically instrumented fetal sheep in utero before and after exposure of pregnant ewes to intense broadband noise. A single 16 hr exposure was delivered at 113 days gestational age, a time when the ABR is just emerging. Thresholds were compared with an age-matched, nonexposed control group. In the second experiment, fetal sheep at the same gestational age were exposed four times to broadband noise and their cochleae were harvested 20 days later for histological analysis by the use of scanning electron microscopy. Comparisons were made with an age-matched, nonexposed control group. RESULTS: Experiment One: ABR thresholds recorded between 10 to 20 days after the exposure were not as sensitive as thresholds obtained from control fetuses. There was a tendency for thresholds to 0.5 kHz tone bursts to be more affected than thresholds to clicks. Experiment Two: Scanning electron microscopy of the organ of Corti from fetuses exposed to noise from 111 to 114 days gestational age revealed significant damage to inner and outer hair cells in the middle and apical turns of cochleae. Similar hair cell damage was not present in control fetuses. CONCLUSIONS: Intense exogenous noise penetrated the uterus of pregnant sheep and resulted in elevations in ABR thresholds 2 to 3 wk after exposure. In fetuses repeatedly exposed to noise, the middle and apical turns of the cochlea showed greater hair cell damage than found at the same locations in control cochlea. The basal turn of the cochlea was not damaged.     

Monoamine release from dopamine-depleted rat caudate nucleus reinnervated by substantia nigra transplants: An in vivo electrochemical study

Previous studies have shown that fetal substantia nigra (SN) transplanted into a cavity overlying a dopamine (DA)-denervated caudate nucleus can reverse a number of the behavioral abnormalities induced by the denervation. While some histochemical and physiological evidence suggests that this reversal is the result of a functional DA input from the transplant to the host brain, there is little direct evidence for transmitter release from ingrowing graft-derived nerve fibers. In the present work in vivo electrochemistry was used to analyse the magnitude, time course and spatial distribution of neurotransmitter releases evoked by local application of potassium (K+) from DA-depleted, SN transplant-reinnervated striatum. Animals were injected unilaterally with 6-hydroxydopamine (6-OHDA) into the SN and screened by measuring apomorphine-induced rotation. Some were then given SN grafts, which were placed in a 'delayed cavity' just dorsal to the lesioned striatum. Nafion-coated graphite epoxy capillary (GEC) electrodes were employed for the electrochemistry to minimize signals derived from ascorbate or acidic DA metabolites. The GEC electrode was fixed to a K+-filled micropipette and this assembly was used to map the caudate nucleus of control, 6-OHDA-treated, and 6-OHDA-treated, grafted animals. The morphometric relationships between striatal recording sites and transplant location were subsequently verified histologically. Releases from striatal sites within 1.0 mm of the SN grafts were slightly, but not significantly, less than those obtained from control caudate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Closed treatment of displaced diaphyseal both-bone forearm fractures in older children and adolescents

The management of adolescent radius and ulna diaphyseal fractures is controversial. The purpose of this study was to address the residual deformity and functional outcome following closed treatment of these fractures. Twenty-five older children and adolescents (mean age 13.3 years, range 8.8-15.5) with displaced diaphyseal both-bone forearm fractures underwent closed treatment and were followed for a mean of 49.6 weeks. All fractures united. On the final AP radiograph, the mean angulation was 9 degrees (range 0-18 degrees) for the radius and 8 degrees (0-20 degrees) for the ulna. All patients achieved full elbow and wrist range of motion. Loss of forearm supination and pronation averaged 4 degrees (range 0 to 20 degrees) and 6.8 degrees (0 to 40 degrees), respectively. Closed reduction and casting of displaced both-bone diaphyseal forearm fractures, despite the residual angulation, results in satisfactory functional outcome and should remain a viable treatment option in the management of this injury.     

Differential effects of cyclosporine and tacrolimus on mycophenolate pharmacokinetics in patients with impaired kidney function

In a single-center prospective randomized controlled study, the impact of calcineurin inhibitor (CNI) reduction or withdrawal on the pharmacokinetics of mycophenolic acid (MPA) was studied in a group of renal transplant recipients with impaired renal function. Mycophenolate mofetil (MMF) was added to a baseline regimen of prednisolone and CNI. Afterwards the patients were randomized into “CNI withdrawal” and “CNI continuation” groups. The dosage of CNIs, cyclosporine or tacrolimus, was gradually reduced and withdrawn within 6 weeks from patients in the withdrawal group. The continuation group was maintained on therapy with CNI, MMF, and steroids. These regimens were maintained until the ninth month. In contrast to the withdrawal of tacrolimus, which has no significant effect on MPA pharmacokinetics, cyclosporine withdrawal was associated with a significant increase in the trough levels and areas under the curve of MPA. Serum creatinine and urine albumine levels stabilized on average after CNI withdrawal in this population. The results are consistent with the hypothesis that cyclosporine attenuates the enterohepatic recirculation of MPA. The withdrawal of CNI has a positive effect on renal function in chronic allograft dysfunction.     

Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor

OBJECT: Glial cell line-derived neurotrophic factor (GDNF) has demonstrated significant antiparkinsonian actions in several animal models and in a recent pilot study in England in which four of five patients received bilateral putaminal delivery. In the present study the authors report on a 6-month unilateral intraputaminal GDNF infusion in 10 patients with advanced Parkinson disease (PD). METHODS: Patients with PD in a functionally defined on and off state were evaluated 1 week before and 1 and 4 weeks after intraputaminal catheter implantation in the side contralateral to the most affected side. Each patient was placed on a dose-escalation regimen of GDNF: 3, 10, and 30 microg/day at successive 8-week intervals, followed by a 1-month wash-out period. The Unified Parkinson's Disease Rating Scale (UPDRS) total scores in the on and off states significantly improved 34 and 33%, respectively, at 24 weeks compared with baseline scores (95% confidence interval [CI] 18-47% for off scores and 16-51% for on scores). In addition, UPDRS motor scores in both the on and off states significantly improved by 30% at 24 weeks compared with baseline scores (95% CI 15-48% for off scores and 5-61% for on scores). Improvements occurred bilaterally, as measured by balance and gait and increased speed of hand movements. All significant improvements of motor function continued through the wash-out period. The only observed side effects were transient Lhermitte symptoms in two patients. CONCLUSIONS: Analysis of the data in this open-label study demonstrates the safety and potential efficacy of unilateral intraputaminal GDNF infusion. Unilateral administration of the protein resulted in significant, sustained bilateral effects.