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Biomedical subjects

R D Penn

Publications and source records attributed to R D Penn.

At least 19 recordsLinked to original sources
PubMed1992

Intrathecal baclofen for spasticity of spinal origin: seven years of experience.

A total of 66 consecutive patients with severe spasticity of spinal cord origin were screened with intrathecal baclofen, and all but two responded with a two-point decrease in their Ashworth spasticity scale and/or spasm scale score. Of these, 62 elected to receive chronic intrathecal baclofen administration by means of an implanted delivery system. These patients have been followed for an average of 30 months (the first three for 81 months). Intrathecal baclofen has been well tolerated and all serious side effects were transient and have been managed by dose adjustments. The pump presently available has worked safely; the only problem has been stalling in 7% of these devices. The catheter system has had to be repaired in just over one-half of the patients and is the main cause of interruption of drug delivery. Of the 62 patients implanted, 52 (84%) continue to be treated adequately for spasticity; there are three poor long-term responders, four deaths due to underlying disease, and three whose participation has been voluntarily withdrawn. It is suggested that long-term control of spinal spasticity by intrathecal baclofen can be achieved in most patients.

Adolescent↗
PubMed1992

Intrathecal baclofen. Effects on nocturnal leg muscle spasticity.

Electromyographic activity was recorded from tibialis anterior during nocturnal polysomnography in six patients with severe spasticity of spinal origin. The patients had a baclofen reservoir system implanted subcutaneously into their lumbar subarachnoid space and were studied for two nights in a double-blind, placebo controlled, crossover design. Tibialis anterior electromyographic activity per hour of sleep was reduced on the night of baclofen infusion. In particular, less electromyographic activity occurred after arousal from sleep.

Adult↗
PubMed1991

Putative chromaffin cell survival and enhanced host-derived TH-fiber innervation following a functional adrenal medulla autograft for Parkinson's disease.

We report heretofore undescribed clinical and histological features of a patient with idiopathic Parkinson's disease who showed marked and persistent motoric benefit from an adrenal medulla autograft for 18 months following grafting. The patient returned to the preoperative level of disability prior to his death 30 months after implantation, the longest survival to date for an adrenal transplant. The graft site was primarily necrotic and large numbers of macrophages were still present at the time of death. A few tyrosine hydroxylase-immunoreactive cells were found within the graft, providing the first evidence that adrenal medullary cells may be viable and produce catecholamines following human transplantation. A dense network of tyrosine hydroxylase-immunoreactive terminals and processes was also seen ventral to the implant site and on both of its lateral borders. This response may represent sprouting by residual host dopaminergic neurons mediated by the vigorous response to injury displayed by the host striatum. The relative paucity of surviving chromaffin cells, however, provides further evidence that adrenal medulla grafts survive poorly following intracerebral implantation, and factors other than dopamine replacement may be responsible for most of the functional effects observed following chromaffin cell transplantation.

Adrenal Medulla↗
PubMed1991

United Parkinson Foundation Neurotransplantation Registry on adrenal medullary transplants: presurgical, and 1- and 2-year follow-up.

Thirteen centers participated in a multicenter database with systematic evaluation of US and Canadian patients who had adrenal medullary transplantation for Parkinson's disease. This voluntary registry collected demographic, safety, and efficacy data using the same scoring measures over a 2-year follow-up period. Baseline data on 61 patients and 2-year follow-up data on 56 patients were compared. Eighteen percent died during the study period, and one-half of these deaths were related or questionably related to the surgery. Of the remaining 45 patients with data, global improvement, defined as an improved summed score of the "on" and "off" motor and activities of daily living functions from the Unified Parkinson's Disease Rating Scale, occurred in 32% of the patients at 2 years after surgery. At follow-up, significant group improvement persisted in the amount of daily "on" time and the quality of "off" function, but other measures were no better than baseline. When the global improvement calculation was based on the total sample and included deaths and patients lost to follow-up as "not improved," only 19% were improved 2 years after surgery. Twenty-two percent of survivors had persistent psychiatric morbidity not present prior to surgery. These data document a modest group improvement in "off" function after neurotransplantation, but a serious level of mortality and morbidity.

Adrenal Medulla↗
PubMed1991

Dopamine distribution and behavioral alterations resulting from dopamine infusion into the brain of the lesioned rat.

In an effort to verify the "dopamine secretion hypothesis" as the mechanism responsible for the antiparkinsonian efficacy of adrenal medullary transplants into the brain, the effects of dopamine infusion into the brains of rats with unilateral substantia nigra lesions were examined. The apomorphine-induced rotation, characteristic of this animal model, was diminished after 7 days of continuous dopamine infusion (10 micrograms/hr) into the ipsilateral striatum, whereas intraventricular infusion was without effect. Chromatographic analysis of the dopamine distribution after 10 days of infusion into either region revealed that ipsilateral delivery of dopamine did not result in contralateral increases in dopamine content. Examination of the adjacent striatum following ipsilateral intraventricular delivery indicated that dopamine had only penetrated 1 mm. Even with intrastriatal delivery, there were still parts of the infused striatum which had below-normal levels of dopamine. The fact that striatal tissue presents a significant barrier to the penetration of dopamine is discussed in relation to adrenal medullary and fetal nigral transplants.

Adrenal Medulla↗
PubMed1990

Autologous transplantation of adrenal medulla in Parkinson's disease. 18-month results.

Eighteen of 19 patients who underwent autologous adrenal medullary transplantation to the right caudate nucleus have been followed up for 18 months. During the course of this study, a statistically significant improvement was noted in percent "on" time, percent "on" time without dyskinesia, activity of daily living (ADL) scores during the "on" stages, and ADL, motor, and Schwab-England scores during the "off" stages. Benefits tended to be maximal at 6 months and to gradually lessen thereafter, although statistically significant improvement in comparison with baseline was still present at 18 months for ADL, motor, and Hoehn-Yahr scores during the "off" stages. Almost all parameters had deteriorated by 18 months compared with 12 months, including those remaining significantly improved in comparison with baseline. These patterns were similar for each of the three participating centers. Complications were largely restricted to the perioperative period.

Adrenal Medulla↗
PubMed1990

Indium-111 DTPA flow study to evaluate surgically implanted drug pump delivery system.

The authors describe a radionuclide technique for evaluating intrathecal and intraventricular infusions by surgically implanted drug pump delivery systems. Sixteen patients underwent flow studies, performed by injecting 500 mu Ci of indium-111 DTPA into the pumps. Early and delayed images were obtained. These studies enabled distinction among functioning pumps, nonfunctioning pumps, and obstructed or occluded catheters. We conclude that indium-111 DTPA flow studies provide an excellent way to assess these drug pump delivery systems.

Equipment Failure↗
PubMed1990

Adrenal medullary transplant to the striatum of patients with advanced Parkinson's disease: 1-year motor and psychomotor data.

We studied motor and psychomotor changes over 1 year after surgery in 7 patients with severe idiopathic Parkinson's disease (PD) who underwent intrastriatal autologous adrenal medulla transplant. Significant clinical improvements were present 1 year after surgery and primarily involved increased quantity of "on" time and increased quality of "off" time: "on" time increased from a mean 60.7% of the waking day to 82.7%, and "off" function improved. In contrast, although "on" function also improved, statistically significant improvement occurred in only 1 measure, the Unified Parkinson's Disease Rating Scale activities of daily living subscale. Medications did not change, and motor fluctuations persisted. Improvement began several weeks after surgery, was maximal at 4 to 6 months, and was sustained thereafter. There was significant group improvement in quality of life measures of sleep and rest, social isolation, and ambulation. One patient had severe, recurrent depression postoperatively. The efficacy of adrenal transplant surgery is not transient, and specific functional improvements can be prolonged.

Activities of Daily Living↗
PubMed1990

Effects of intrathecal baclofen on voluntary motor control in spastic paresis.

Intrathecal baclofen injections were given to six patients with long-standing spastic paresis resistant to any nondestructive treatment, including oral baclofen. Attempts by the patients at voluntary muscle activation before intrathecal administration of baclofen led to considerable uncontrolled coactivation of antagonist and distant muscles. After the injection, dramatic suppression of the spastic signs was accompanied by more selective voluntary muscle activation. Tonic coactivation of the antagonists and distant muscle groups during voluntary contractions was decreased while the agonist level on electromyography (EMG) was not affected (three cases) or only slightly reduced (three cases). Furthermore, in one patient with sufficient residual motor control function, there was a considerable increase in the speed of fast isotonic movements, accompanied by the emergence of the ability to generate phasic muscle bursts on EMG that were characteristic of normal motor patterns. The results suggest that baclofen exerts different effects upon reflex pathways and descending motor pathways. This therapy appears to be a promising way for improving residual motor control in patients with increased muscle tone and/or reflexes.

Baclofen↗
PubMed1990

Medical and surgical treatment of spasticity.

Significant advances in the medical and surgical treatment of spasticity have occurred over the last decade. These improvements in treatment and the previous work on which they are based are presented. In particular, Foerster's pioneering observations and the neuropharmacology of antispastic drugs are discussed.

Baclofen↗
PubMed1989

Intrathecal baclofen for severe spinal spasticity.

We studied the effect of the intrathecal infusion of baclofen, an agonist of gamma-aminobutyric acid, on abnormal muscle tone and spasms associated with spinal spasticity, in a randomized double-blind crossover study. Twenty patients with spinal spasticity caused by multiple sclerosis or spinal-cord injury who had had no response to treatment with oral baclofen received an intrathecal infusion of baclofen or saline for three days. The infusions were administered by means of a programmable pump implanted in the lumbar subarachnoid space. Muscle tone decreased in all 20 patients (mean [+/- SD] Ashworth score for rigidity, from 4.0 +/- 1.0 to 1.2 +/- 0.4; P less than 0.0001), and spasms were decreased in 18 of the 19 patients who had spasms (mean [+/- SD] score for spasm frequency, from 3.3 +/- 1.2 to 0.4 +/- 0.8; P less than 0.0005). Tests for motor function, neurologic examination, and assessments by the patients correctly indicated when baclofen was being infused in all cases. All patients were then entered in an open long-term trial of continuous infusion of intrathecal baclofen. During a mean follow-up period of 19.2 months (range, 10 to 33), muscle tone has been maintained within the normal range (mean Ashworth score, 1.0 +/- 0.1) and spasms have been reduced to a level that does not interfere with activities of daily living (mean spasm score, 0.3 +/- 0.6). No drowsiness or confusion occurred, one pump failed, and two catheters became dislodged and had to be replaced. No infections were observed. Our observations suggest that intrathecal baclofen is an effective long-term treatment for spinal spasticity that has not responded to oral baclofen.

Adult↗
PubMed1989

Multicenter study of autologous adrenal medullary transplantation to the corpus striatum in patients with advanced Parkinson's disease.

In 19 patients with severe Parkinson's disease, we replicated the surgical procedures developed by Madrazo et al. for transplantation of the adrenal medulla to the striatum, and followed them for six months after operation. We monitored their motor function with the use of standardized scales and determined the amount and quality of "on" and "off" time (the hours of the waking day when the antiparkinsonian medications were effective and ineffective, respectively). We found significant improvement in focal areas of motor function. The mean percentage of on time during the day increased from 47.6 percent to 75.0 percent (P = 0.012); the mean percentage of on time without chorea increased from 26.6 percent to 59.2 percent (P = 0.006); the mean severity of off time decreased as assessed by both the Activities of Daily Living subscale of the Unified Parkinson's Disease Scale (P = 0.002) and the Schwab and England scale (P = 0.037). In contrast to the finding of Madrazo et al., however, the dosages of antiparkinsonian medications could not be decreased and postoperative morbidity was substantial. Despite cautious optimism, we conclude that the widespread use of this procedure outside of research centers is premature, since the improvement we found was slighter than in the previous cases.

Activities of Daily Living↗
PubMed1989

Short-term effects of intrathecal baclofen in spasticity.

Six patients with long-lasting spasticity resistant to different drug therapies including oral baclofen received a bolus injection of lumbar intrathecal baclofen. Electromyographic (EMG) reactions of leg muscles (soleus, tibialis anterior, quadriceps, and hamstrings) to standard stimuli and during attempts at voluntary activation were recorded before the drug injection and up to 3 h after the injection. Responses to joint movements, H-reflexes, ankle clonus, and defensive reactions were noticeably suppressed within 30-45 min after the injection and had practically disappeared after 2 h. Ankle clonus was seen only in patients with H-reflexes, and clonus disappeared when the reflex responses to the n. tibialis stimuli were absent. A decrease in clonus EMG burst amplitudes was accompanied by a decrease in the clonus frequency. These observations favor the autooscillation hypothesis of clonus. Baclofen injection led to improvement in selective voluntary activation of leg muscles in patients with residual motor control. These results suggest that execution of voluntary motor commands in the patients suffered from functionally abnormal spinal circuitry rather than from changes in the descending motor commands. Intrathecal baclofen appears to be an effective way of eliminating increased muscle tone and spasms which can allow for voluntary motor function when it is present.

Administration, Oral↗
PubMed1989

Chronic access to endoneurial space using an arterial autograft.

A technique for direct chronic infusion of compounds onto peripheral axons has been investigated in the rat sciatic nerve. A 2 cm segment of the femoral artery was removed and one end inserted into the endoneurial space of the contralateral peroneal nerve fascicle of the same animal. The other end of the artery was connected to a catheter system to allow infusion into the endoneurium, thus bypassing the barrier that the perineurium presents to hydrophilic compounds. The patency of this arterial access system was evaluated by the ability of 20 microliters of 2% lidocaine to inhibit the toe-spreading reflex. The results of the study were that the infusion system remained operational for 3-7 days after transplantation. There were histologic changes in the nerve but there were no functional deficits due to the surgery. Although a long-term endoneurial infusion was not achieved, the limited access time to the axons might be long enough for applications such as the delivery of nerve growth factors to injured nerve.

Animals↗