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T L Munsat

Publications and source records attributed to T L Munsat.

At least 73 records · Page 4Linked to original sources
PubMed1988

Spinal cord TRH deficiency is associated with incomplete recovery of denervated muscle in the rat.

The raphe-spinal pathway, which contains co-localized serotonin (5-HT), thyrotropin-releasing hormone (TRH), and several TRH-prohormone-derived non-TRH peptides, projects to the ventral horn of the spinal cord. Pharmacologic ablation of this pathway with the 5-HT neurotoxin, 5,7-dihydroxytryptamine, in neonatal rats resulted in deficient recovery of plantar foot muscles, functionally denervated with botulinum toxin type A. Failure of reinnervation was suggested by slower and incomplete recovery of the plantar foot compound muscle action potential amplitude and by a reduced mean diameter of plantar foot muscle fibers in ablated rats. These findings indicate that deprivation of alpha motor neurons from descending raphe-spinal input interferes with their ability to respond to muscle-derived signals for reinnervation.

5,7-Dihydroxytryptamine↗
PubMed1987

Effect of spinal cord TRH deficiency on lower motorneuron function in the rat.

Thyrotropin-releasing hormone (TRH), present in high concentrations in the mammalian spinal cord, exerts excitatory effects on the alpha-motorneuron (AMN) via axodendritic contacts. We used the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) to deplete TRH from the ventral horn of the spinal cord of adult rats to determine whether the tripeptide may be trophic to the AMN. The rats were studied blindly and sequentially for 11 weeks. Motor performance remained normal by clinical and electrophysiologic assessments. AMN counts were not reduced in the lumbar cord, and gastrocnemius muscle showed no evidence of denervation in treated rats. We conclude that in the adult rat chronic ventral horn TRH deficiency does not lead to AMN degeneration and is not associated with a significant alteration of AMN function.

5,7-Dihydroxytryptamine↗
PubMed1987

Pharmacokinetics of intrathecal thyrotropin-releasing hormone.

An investigation of the efficacy of thyrotropin-releasing hormone in amyotrophic lateral sclerosis included study of the intrathecal pharmacokinetics of this neuropeptide. Its mean elimination half-life in CSF was 0.90 hours and was monoexponential. During a 2-hour infusion, 2.75% crossed the CSF/blood-brain barrier. Infusion for 12 months with an implanted pump in three patients at a rate of 3 mg/24 hr resulted in a mean CSF steady state of 2.88, 2.42, and 2.74 micrograms/ml, respectively. Pharmacokinetic data were similar at 6 and 12 months. This is an effective system with potential uses in the treatment of other degenerative diseases.

Amyotrophic Lateral Sclerosis↗
PubMed1987

Intrathecal thyrotropin-releasing hormone in amyotrophic lateral sclerosis.

Thyrotropin releasing hormone (TRH) has potential therapeutic applications in amyotrophic lateral sclerosis (ALS) and related diseases because of its function as a neuroregulator of the anterior horn cell. However, its therapeutic potential, and that of other neuropeptides, is reduced by the blood-brain barrier that limits access to neuronal cells. We have thus explored the direct intrathecal administration of TRH in ALS, with both short-term boluses and infusions and chronic constant infusions. Our experience suggests that this approach is safe, has high patient acceptance, and is worthy of more careful evaluation.

Amyotrophic Lateral Sclerosis↗
PubMed1987

Quantitative assessment of neuromuscular deficit in ALS.

Several criteria must be met in developing a test battery forr ALS. First, the test items should be designed to answer the specific questions being asked. If questions involve the amount and rate of deterioration, then the test items should generate interval data and show evidence that they reflect change in the disease itself. Second, the reliability of the test items should be carefully determined. Are the variances due to testing errors such as inconsistent positioning or changes in verbal instructions; or do they reflect human performance variation? Third, the test items must be sensitive to small changes, and one must be able to test the very strong as well as the severely debilitated patient. The TQNE was designed to measure degree of disease progression in ALS. The major portion of the protocol consists of isometric force measurement using an electronic strain gauge. Other quantitative segments include tests of pulmonary function, speech rates, and timed activities. Using z-score transformations, we have summarized these test items into five megascores: pulmonary function, bulbar function, timed hand activities, arm strength, and leg strength. Megascores have been used to characterize the natural history of the disease and to judge therapeutic efficacy. Quantitative methods to measure deficit in neuromuscular disease lag far behind other technologic advances in medical research. Future advances in the measurement of neuromuscular deficit depend on the commitment of researchers to invest the time and resources necessary to develop more sensitive and reliable testing techniques.

Amyotrophic Lateral Sclerosis↗
PubMed1986

Sustained rises in serum thyrotropin, thyroxine, and triiodothyronine during long term, continuous thyrotropin-releasing hormone treatment in patients with amyotrophic lateral sclerosis.

In a pilot therapeutic trial, four patients with amyotrophic lateral sclerosis (ALS) were treated with long term, continuous infusions of TRH, three intrathecally and one epidurally. They had prompt increases in serum TSH and thyroid hormone concentrations, averaging 120% for TSH, 49% for serum T4, 68% for the serum free T4 index, 49% for serum T3, and 67% for the serum free T3 index. These elevations were statistically significant for all but serum T3 and persisted for the duration of treatment (4-7 months). Mean values during treatment were near the upper limit of normal for each of these hormone measurements. After TRH withdrawal, serum TSH fell transiently below the normal range. A comparison group of four patients with ALS treated by twice weekly intrathecal bolus doses of TRH had no significant changes in serum TSH, T4, or T3. During continuous TRH treatment, the responsiveness of both TSH and PRL to a standard iv TRH stimulation test was blunted, but not abolished. Basal serum PRL was occasionally elevated in the two women during continuous TRH treatment, but was normal in the men, and serum GH was normal in all patients. In the patients receiving continuous TRH treatment, indexes of end-organ effects of thyroid hormone were inconclusive; none had a rise in serum ferritin, one of four had a rise in serum sex hormone-binding globulin, and three had increased creatinuria. These results provide direct evidence in man that chronic TRH administration can cause modest sustained increases in serum TSH and thyroid hormones, though the metabolic consequences of these changes are uncertain, and appears to raise the set-point of the pituitary-thyroid axis, i.e. the serum T4 and T3 concentrations needed for a given degree of suppression of basal TSH secretion.

Amyotrophic Lateral Sclerosis↗
PubMed1986

Familial amyloidosis with cranial neuropathy and corneal lattice dystrophy.

A 64-year-old woman had bilateral facial weakness, mild peripheral neuropathy, incoordination, and impaired balance. A corneal transplant had been performed for corneal lattice dystrophy. Sural nerve biopsy showed mild axonal neuropathy with deposits of amyloid in the perineurium. Histochemical studies showed amyloid protein AA in the nerve, but not in cornea or muscle.

Adult↗
PubMed1986

Quantitative motor assessment in amyotrophic lateral sclerosis.

Reliable measurements are needed to document the natural history of ALS and to determine therapeutic efficacy. We have devised a standardized protocol that generates interval data sensitive to change-the Tufts Quantitative Neuromuscular Exam (TQNE). The TQNE consists of the following four major categories: pulmonary function, oropharyngeal function, timed functional activities, and isometric strength using an electronic strain gauge. The 29-item exam takes about 1 hour to administer and has excellent test-retest reliability.

Adult↗
PubMed1986

Intrathecal administration of natural human interferon alpha in amyotrophic lateral sclerosis.

Ten patients with amyotrophic lateral sclerosis were given intrathecal injections of natural interferon alpha, 1 million units weekly for 7 to 24 weeks. Six patients completed the trial. Four voluntarily withdrew after 7 to 13 injections. The slopes of deterioration for 40 quantitative tests of neuromuscular function for the control and treatment periods were compared by paired t test in the six patients who completed the trial and in the patient who withdrew after 13 injections. No significant differences were found. The patients tolerated treatment well. The CSF reaction was modest and spontaneously reversible. Indomethacin and ibuprofen blocked interferon side effects.

Amyotrophic Lateral Sclerosis↗
PubMed1986

Amyotrophic lateral sclerosis: thyrotropin-releasing hormone and histidyl proline diketopiperazine in the spinal cord and cerebrospinal fluid.

In spinal cords from seven amyotrophic lateral sclerosis (ALS) patients and four controls, we found no difference in thyrotropin-releasing hormone (TRH) concentration relative to protein content, but there was a reduction per tissue wet weight in ALS. Immunohistochemical localization of TRH in ALS cord was unaltered. Histidyl proline diketopiperazine (HisPro-DKP), a possible metabolite of TRH, was significantly elevated per protein content in ALS. CSF levels of TRH and HisPro-DKP were unchanged. These findings suggest that TRH neurons are not primarily affected in ALS, but TRH and tissue protein are lost together as the disease progresses.

Aged↗
PubMed1986

Total body irradiation not effective in inclusion body myositis.

Four patients with inclusion body myositis were treated with 150 rad of total body irradiation given in 5 weeks. One patient responded subjectively and transiently, but no patient showed clear benefit. This treatment is not recommended for inclusion body myositis.

Adult↗
PubMed1985

Neuromuscular transmission defect in inherited polyneuropathy.

A 51-year-old woman with an inherited polyneuropathy had fatiguability and a dramatic historical response to prostigmine. Repetitive motor nerve stimulation produced a prominent decrement of the compound muscle action potential in distal muscles with marked facilitation after brief exercise. Defective neuromuscular transmission paralleled the polyneuropathy in distribution and severity. We hypothesize that deficient release of acetylcholine by regenerating or degenerating nerve terminals likely caused the defect of neuromuscular transmission in this patient.

Electromyography↗
PubMed1984

A double-blind controlled trial of bovine brain gangliosides in amyotrophic lateral sclerosis.

We conducted a double-blind controlled study of the effect of brain gangliosides in amyotrophic lateral sclerosis. Nineteen patients received intramuscular gangliosides (40 mg/d) for 6 months, and 21 received placebo. The deterioration rates for approximately 120 clinical and electrophysiologic parameters of neuromuscular function were analyzed, but no statistically significant beneficial effect of the drug was demonstrated. However, the large coefficient of variation for each item indicated that a sample size of several hundred patients would have been necessary to exclude the possibility that the drug produced a 25% slowing of progression of the disease.

Amyotrophic Lateral Sclerosis↗