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Biomedical subjects

L H Phillips

Publications and source records attributed to L H Phillips.

At least 37 records · Page 2Linked to original sources

Amyotrophic lateral sclerosis: serum factors enhance spontaneous and evoked transmitter release at the neuromuscular junction.

Sera from 30 patients with sporadic amyotrophic lateral sclerosis (ALS) were tested to determine their effects at the neuromuscular junction. Spontaneous transmitter release was significantly increased, as evidenced by a 151% increase in MEPP frequency, by sera from 16 ALS patients. In addition, 16 patients' sera elevated EEP quantal content by an average of 89%. Eleven sera produced both effects. There was no consistent change in MEPP amplitude or time course, indicating the absence of a humoral effect on postjunctional ACh receptors or endplate membrane function. These results suggest that a portion of the sporadic ALS patient population possess serum factors that can alter presynaptic function of the motor nerve terminal. Evidence from the present experiments indicates that alterations at the neuromuscular junction are a result of a combination of increased Ca2+ influx into the cell and an independent increase in intracellular calcium concentration.

Amyotrophic Lateral Sclerosis↗

Mitochondria in sporadic amyotrophic lateral sclerosis.

Mitochondria are abnormal in persons with amyotrophic lateral sclerosis (ALS) for unknown reasons. We explored whether aberration of mitochondrial DNA (mtDNA) could play a role in this by transferring mitochondrial DNA (mtDNA) from ALS subjects to mtDNA-depleted human neuroblastoma cells. Resulting ALS cytoplasmic hybrids (cybrids) exhibited abnormal electron transport chain functioning, increases in free radical scavenging enzyme activities, perturbed calcium homeostasis, and altered mitochondrial ultrastructure. Recapitulation of defects previously observed in ALS subjects and ALS transgenic mice by expression of ALS mtDNA support a pathophysiologic role for mtDNA mutation in some persons with this disease.

1-Methyl-4-phenylpyridinium↗

Effects of seasonal change in rugby league on the incidence of injury.

OBJECTIVES: To assess the effects that the recent seasonal change in rugby league from winter to summer has had on the incidence of injury. METHODS: All injuries that occurred during games and training were recorded throughout four consecutive seasons (three winter, one summer) for the first team squad of a British professional rugby league club. Data included nature of injury, days lost as the result of injury, player position, month, and season. RESULTS: An increasing incidence of injury over the four seasons was observed, with the summer seasons having an incidence almost double that of the first winter season recorded (696.8 per 1000 hours and 363.55 per 1000 hours respectively). The severity of injury was shown to decline over the four seasons. Most injuries were incurred in matches (74.9%) rather than during training (25.1%). CONCLUSIONS: The findings show an increasing incidence of injury in summer rugby but with decreased severity. It is not known if this is the result of playing back to back rugby seasons or is a consequence of a change in playing season and ground conditions.

Adult↗

The role of electrodiagnostic testing in carpal tunnel syndrome.

Electrodiagnostic testing in patients who have upper-extremity symptoms, which may include carpal tunnel syndrome (CTS), has been the gold standard for diagnosis for many years. Despite their value, these tests are underutilized. The authors examined the use patterns of electrodiagnostic testing at the University of Virginia by reviewing the records of the Electromyography Laboratory for the calendar year 1994. Studies in patients with CTS comprised 15% of the 1626 studies performed during that time. The mononeuropathy was mild in the majority of cases and most of the patients were referred for testing by specialists. There was a clear referral bias on the part of the primary care physicians, and the severity of mononeuropathy in the patients they referred for testing was significantly greater than in patients referred by specialists.

Journal Article↗

cis Elements and trans factors are both important in strain-specific regulation of the leukotoxin gene in Actinobacillus actinomycetemcomitans.

Actinobacillus actinomycetemcomitans, the etiologic agent of localized juvenile periodontitis, produces a potent leukotoxin that kills human neutrophils. The production of leukotoxin RNA can vary more than 50-fold among isolates of A. actinomycetemcomitans, and strains expressing high levels of leukotoxin RNA are most often found at sites of periodontal disease. To assess the relative contributions of transcription factors and promoter sequences in setting the disparate levels of leukotoxin RNA found, we have undertaken classical cis/trans analyses. First, the leukotoxin promoter regions from moderately leukotoxic (Y4) and minimally leukotoxic (ATCC 33384) strains of A. actinomycetemcomitans were cloned, sequenced, and compared with the previously sequences leukotoxin promoter region of the high-producer strain JP2. The Y4 and ATCC 33384 promoter regions each contain a 528-bp segment that is absent from JP2. Interestingly, the analysis of various deletion constructs in A. actinomycetemcomitans indicated that Y4, despite the large insertion, initiates leukotoxin RNA synthesis at the same promoter as JP2 does. To perform cis/trans analyses, these three leukotoxin promoter regions were cloned into a plasmid upstream of the reporter gene beta-galactosidase. Each plasmid was transformed into JP2, Y4, and ATCC 33384, and the beta-galactosidase levels were determined. The results indicated that the sequences responsible for down-regulating leukotoxin RNA levels in Y4 relative to JP2 are found within the transcribed region of the Y4 leukotoxin operon. Importantly, in ATCC 33384, strain-specific trans factors and promoter sequence differences are equally significant in determining the lower levels of leukotoxin RNA. We hypothesize that either strain ATCC 33384 has a negative regulatory protein (which is missing or mutated in JP2/Y4) or that JP2 and Y4 carry an activator that is missing or mutated in ATCC 33384.

Aggregatibacter actinomycetemcomitans↗

Epidemiologic evidence for a changing natural history of myasthenia gravis.

OBJECTIVE: To survey the epidemiologic literature for evidence of an increasing prevalence of myasthenia gravis (MG) over time, and to explore the reasons for the increase. DATA SOURCES: We found population-based reports of the epidemiology of MG by searching bibliographic databases. We used MG, epidemiology, prevalence, incidence, and mortality as search terms. STUDY SELECTION: We included population-based studies that reported the number of cases and the time period from which rates were calculated. STATISTICAL METHODS: We performed a regression analysis of rates versus date of study, comparing the slopes of regression lines for prevalence, incidence, and mortality. We performed a second analysis grouping rates by decade of study and calculating a mean rate weighted by the size of the population studied. We calculated 95% confidence intervals for each rate. RESULTS: We included 33 studies from 1950 through 1995. Prevalence and incidence rates increased over time, but the regression line for prevalence significantly exceeded that for incidence. Mortality rates declined slightly. The weighted means for prevalence rose significantly, but there was no significant change in incidence or mortality. CONCLUSION: The prevalence of MG has increased over the past forty-five years, probably because patients with the disease have longer life spans owing to present-day treatment.

Adult↗

Direct spinal stimulation for intraoperative monitoring during scoliosis surgery.

Intraoperative electrophysiological monitoring of the spinal cord has traditionally been done by recording somatosensory evoked potentials (SEP). There is a risk that SEPs can be unaltered when significant injury to the anterior spinal cord has occurred. The purpose of this report is to describe a simple technique for intraoperative spinal cord stimulation which monitors descending pathways in the anterior spinal cord. Stimulation occurs through needle electrodes inserted into spinous processes in the rostral surgical wound, and recordings are made from electrodes in the popliteal spaces. We report our experience in monitoring spinal instrumentation in 45 patients with idiopathic scoliosis and 20 with some form of neurological disease causing scoliosis. The neurogenic motor evoked potentials (NMEP) are stable and easily recorded from the popliteal spaces in the majority of patients. We describe the case of 1 patient with Friedreich's ataxia in whom no SEPs could be recorded, but NMEPs were used successfully for monitoring. We have fond that combining traditional SEP monitoring with NMEP recording provides a safe and effective method to monitor the spinal cord during surgical procedures where it is at risk.

Adolescent↗

A comparison between IVIg and plasma exchange in Guillain-Barré syndrome: a review and decision analysis of the two treatment modalities.

Plasma exchange (PE) has been established as an effective treatment for Guillain-Barré syndrome (GBS), and until recently, was the only treatment significantly to modify the disease course. Data from a recently published Dutch study suggest that intravenous immunoglobulin (IVIg) is as effective as PE in improving the speed of recovery and lessening disability. Recent small case series in the United States have shown unexpectedly high relapse rates in patients with GBS treated with IVIg. At present, clinicians face a dilemma in choosing between the two options, because there is uncertainty about the efficacy and relapse rate associated with IVIg. In this article, we perform a decision analysis that takes into account the efficacy of therapy, relapse rates, and patient preferences with respect to particular outcomes. Although both modalities are quite costly, an economic analysis shows a slight cost advantage for IVIg. Plasma exchange remains to preferred treatment, based on a decision analysis and currently available data. Results of future IVIg trials can be compared to the PE data using the decision-analysis model.

Decision Support Techniques↗

Directed genomic integration in Actinobacillus actinomycetemcomitans: generation of defined leukotoxin-negative mutants.

To develop targeted gene integration in the periodontal pathogen Actinobacillus actinomycetemcomitans, a ColE1-based, spectinomycin-resistant plasmid containing a segment of the leukotoxin gene was electroporated into strain JP2. In all of the stable spectinomycin-resistant transformants that arose, the plasmid had recombined into the genomic leukotoxin locus since ColE1-based vectors cannot replicate extrachromosomally in A. actinomycetemcomitans. Directed genomic integration was then used to construct a leukotoxin-negative strain by transforming the leukotoxin-producing strain JP2 with a ColE1-based plasmid containing an internal fragment of the leukotoxin gene. Cytotoxicity assays proved that these transformants had < 0.1% of the leukotoxin activity of the parental strain. These results demonstrate that integration-based approaches can be used for generating isogenic mutants in specific virulence genes in A. actinomycetemcomitans.

Aggregatibacter actinomycetemcomitans↗

Effects of selective dorsal rhizotomy for spastic diplegia on hip migration in cerebral palsy.

In spastic diplegia of cerebral palsy, migration of the femoral head beyond a lateral edge of the acetabulum is a common orthopedic deformity and requires surgical treatment. We investigated whether selective dorsal rhizotomy for spastic diplegia halts or exacerbates lateral hip migration. The Reimers migration percentage computed from preoperative and postoperative hip radiographs was used as an index of the severity of lateral hip migration in all 134 hips of 67 children examined. At the time of rhizotomy, 38 patients were between 2 and 4 years of age and 29 were between 5 and 11 years of age. The follow-up period ranged from 6 to 10 months in 20 patients and from 15 to 46 months in 47 patients. Overall, the MP remained unchanged in 75% decreased in 17% and increased in 7%; thus, 93% of all hips examined were stable radiographically. Although most patients experienced postoperative hip stability, there was a significant trend for patients with greater preoperative migration to show decreased postoperative migration. The preoperative ambulatory status of patients had no impact on hip stability after dorsal rhizotomy. By the last follow-up, only 1 patient had undergone orthopedic operations for a persistent hip deformity. The results suggest that in children with spastic diplegia, selective dorsal rhizotomy halts lateral hip migration in the great majority of cases.

Adolescent↗

The epidemiology of myasthenia gravis.

This review has attempted to show what the patient population with MG really looks like. Generalizations about the manifestations of the disease may not be accurate if they are derived from small numbers of patients. The epidemiologic "big picture" provides a more realistic overview of the disease. There are surprisingly fewer patients with MG than many experienced clinicians expect. This does not diminish the impact of the disease on the individual patient, but it does give a more realistic view of its place among diseases affecting the nervous system. This knowledge can be used to direct the approach to the disease in the future. The fact that the number of patients with the disease is increasing in older age groups is a tribute to the success of treatment strategies during the past 20 years. As a consequence, the typical patient with MG in the future will likely be older and have additional medical problems. The evolution of our treatment in the future will need to take this factor into consideration. Older patients may not tolerate the aggressive immunosuppressive regimens that benefit young patients. Ideally, more targeted types of therapies that suppress a specific immunologic abnormality without imposing the burden of side effects inherent in present treatments will be most beneficial to these patients.

Age Factors↗

Anomalous origin of the sural nerve in a patient with tibial-common peroneal nerve anastomosis.

Recognition of anomalous innervation patterns may be important in dealing with peripheral nerve injuries. We describe a patient who suffered injury to the common peroneal nerve (CPN) at the knee when he laterally dislocated his knee. Intraoperative nerve conduction studies during surgical exploration revealed that nerve fibers from the tibial nerve crossed over to join the CPN immediately distal to a neuroma incontinuity. The sural nerve was also found to arise totally from the CPN.

Adult↗

Electrophysiological mapping of the segmental innervation of the saphenous and sural nerves.

Delineation of an area of sensory loss is often helpful in localizing a lesion at the spinal or root level. We have studied the segmental innervation of two cutaneous nerves, the saphenous and the sural, during selective posterior rhizotomy. Each nerve was stimulated electrically, and recordings were made from dorsal roots L-3 to S-2 in 30 patients. We found that both nerves received innervation through at least three spinal levels. The level of maximum innervation was approximately equally divided between L-3 and L-4 for the saphenous nerve. The sural nerve received maximum innervation through S-1 in 80% of the cases, but the remainder came through L-5 or S-2. These findings provide electrophysiologic evidence that these cutaneous nerves have multiple segmental supply, and the sensory area they supply does not lie solely within a single dermatome.

Denervation↗

Sarcoid myopathy presenting with diaphragm weakness.

Sarcoidosis involving muscle occurs frequently, but it is infrequently symptomatic. The clinical, electromyographic, and histologic features of sarcoidosis involving muscle in a 63-year-old woman presenting with diaphragm weakness are described. An electromyogram revealed wide-spread myotonia and an inflammatory myopathic process, suggestive of adult-onset acid maltase deficiency disease. Muscle biopsy showed noncaseating granulomas consistent with sarcoidosis. Clinical improvement followed the initiation of oral prednisone therapy. This case illustrates that muscular sarcoidosis may mimic adult-onset acid maltase deficiency in both its clinical and electromyographic features.

Biopsy↗

Are nerve conduction studies useful for monitoring the adequacy of renal dialysis?

When hemodialysis was first used clinically, a peripheral neuropathy frequently emerged. The discovery that sufficient dialysis time would prevent the emergence of symptomatic neuropathy led to the routine use of nerve conduction studies (NCS) to monitor the "adequacy" of dialysis. Modern dialysis practice has evolved since then, and the patient population is markedly different. This report addresses the question of whether there is evidence to indicate that routine use of NCS is helpful to monitor the adequacy of present-day dialysis. A critical review of the available literature reveals that there is insufficient evidence to allow one to answer the question.

Health Care Costs↗