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Robert G Miller

Publications and source records attributed to Robert G Miller.

18 recordsLinked to original sources
PubMed2006

MCP-1 chemokine receptor CCR2 is decreased on circulating monocytes in sporadic amyotrophic lateral sclerosis (sALS).

Recent studies suggest that monocyte activation may play a role in ALS pathogenesis. Therefore, monocyte CCR2, the receptor for monocyte chemoattractant protein-1 (MCP-1), and plasma levels of MCP-1 were measured in 42 sALS patients, 38 healthy and 34 age-related macular degeneration (ARMD) controls. MCP-1 was elevated in both sALS and ARMD patients, but CCR2 levels were significantly decreased on sALS but not on ARMD monocytes. Loss of monocyte CCR2 expression was inversely correlated with degree of monocyte/macrophage activation in sALS and this decrease was unlikely due to receptor down-regulation given the ARMD results. Defective monocyte/macrophages may play an active role in sALS.

Aged↗
PubMed2006

Fatigue and therapeutic exercise.

Fatigue is a common symptom in patients with neurologic disease. Mechanisms of fatigue are still incompletely understood. In this paper, we review recent studies of fatigue in common neurologic conditions and discuss therapeutic interventions. In particular, the role of therapeutic exercise is examined in both health and disease.

Aging↗
PubMed2006

Factors correlated with NPPV use in ALS.

In spite of emerging evidence of therapeutic benefit from non-invasive positive pressure ventilation (NPPV), only a minority of ALS patients use this therapy. We examined factors which correlate with use of NPPV in ALS patients. Data were analyzed from the ALS CARE Database on the use of NPPV in patients with FVC less than 50% of predicted and probable or definite ALS based on modified El Escorial criteria. Of the 403 eligible patients, 146 (36%) used NPPV. NPPV compliance was strongly correlated with symptoms of dyspnea and orthopnea as well as with the use of other therapies including PEG tubes, augmentative speech devices, and riluzole. Male gender and household income >$80,000 were also associated with higher NPPV use. There was no correlation between age, race, type of insurance, forced vital capacity, duration of symptoms, ALSFRS-R, caregiver burden or quality of life with the use of NPPV. These data suggest that the factors which are most closely associated with NPPV utilization are symptomatic orthopnea and dyspnea. The findings may be useful in designing prospective studies to examine the factors which might explain the underutilization of NPPV and the optimal use of this treatment.

Adult↗
PubMed2005

Distal symmetrical polyneuropathy: a definition for clinical research. A report of the American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation.

The objective of this report was to develop a case definition of "distal symmetrical polyneuropathy" to standardize and facilitate clinical research and epidemiologic studies. A formalized consensus process was employed to reach agreement after a systematic review and classification of evidence from the literature. The literature indicates that symptoms alone have relatively poor diagnostic accuracy in predicting the presence of polyneuropathy; signs are better predictors of polyneuropathy than symptoms; and single abnormalities on examination are less sensitive than multiple abnormalities in predicting the presence of polyneuropathy. The combination of neuropathic symptoms, signs, and electrodiagnostic findings provides the most accurate diagnosis of distal symmetrical polyneuropathy. A set of case definitions was rank ordered by likelihood of disease. The highest likelihood of polyneuropathy (useful for clinical trials) occurs with a combination of multiple symptoms, multiple signs, and abnormal electrodiagnostic studies. A modest likelihood of polyneuropathy (useful for field or epidemiologic studies) occurs with a combination of multiple symptoms and multiple signs when the results of electrodiagnostic studies are not available. A lower likelihood of polyneuropathy occurs when electrodiagnostic studies and signs are discordant. For research purposes, the best approach to defining distal symmetrical polyneuropathy is a set of case definitions rank ordered by estimated likelihood of disease. The inclusion of this formalized case definition in clinical and epidemiologic research studies will ensure greater consistency of case selection.

Electrodiagnosis↗
PubMed2005

Promoting excellence in end-of-life care in ALS.

The type and quality of end-of-life care varies greatly in ALS; the time to initiate end-of-life care is not defined, and decision making is hampered by logistical and financial barriers. There has been no systematic review of these issues in ALS. The goals of this initiative are to: 1) improve end-of-life care for patients with ALS and families based on what limited evidence is available; 2) increase awareness, interest, and debate on the end-of-life care in ALS; and 3) identify areas needed for new prospective clinical research. The ALS Peer Workgroup reviewed the literature and 1) identified the current state of knowledge, 2) analysed the gaps in care, and 3) provided recommendations for standard of care and future research. It was shown that areas of investigation are needed on the incorporation of an interdisciplinary approach to care in ALS that includes: psychosocial evaluation and spiritual care; the use of validated instruments to assess patient and caregiver quality of life; and the establishment of proactive caregiver programs. Several public policy changes that will improve coverage for medical care, hospice, and caregiver costs are also reviewed. More clinical evidence is needed on how to provide optimal end-of-life care specifically in ALS.

Advance Care Planning↗
PubMed2004

Evidence for systemic immune system alterations in sporadic amyotrophic lateral sclerosis (sALS).

Sporadic amyotrophic lateral sclerosis (sALS) is a progressive neuroinflammatory disease of spinal cord motor neurons of unclear etiology. Blood from 38 patients with sALS, 28 aged-match controls, and 25 Alzheimer's disease (AD) patients were evaluated and activated monocyte/macrophages were observed in all patients with sALS and AD; the degree of activation was directly related to the rate of sALS disease progression. Other parameters of T-cell activation and immune globulin levels showed similar disease associated changes. These data are consistent with a disease model previously suggested for AD, wherein systemic immunologic activation plays an active role in sALS.

Adult↗
PubMed2004

"You have shown me my end": attitudes toward presymptomatic testing for familial amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a lethal degenerative motor neuron disease. Approximately, 5-10% of cases of ALS are familial (FALS), inherited primarily as an autosomal dominant trait. Recently, mutations in Cu/Zn superoxide dismutase (SOD1) have been identified; 15-20% of familial cases carry this mutation, providing a marker for diagnosis, carrier testing, and prenatal detection. We assessed understanding of genetics of FALS in relatives of patients cared for at the Forbes Norris MDA/ALS Research Center in San Francisco. A total of 25 participants completed a questionnaire and semistructured interview. Of these, 60% would have gene testing for themselves; 36% believed testing of children or adolescents was a good idea. Overall knowledge of genetics of FALS was limited. Also, 24% of respondents understood the inheritance pattern of FALS; 64% were aware that not all individuals who had the gene would show symptoms in their lifetime. Families were confused about whether they would receive results from linkage studies. We recommend that: (1) physicians refer relatives of newly diagnosed individuals for genetic counseling and possibly psychological counseling; (2) investigators ensure that participants comprehend the purpose of gene identification is for research, not disclosure of individual results; (3) families be helped to understand how to keep abreast of medical and genetic advances; (4) following the model of Huntington disease (HD), consensus guidelines for FALS genetic counseling and testing be developed.

Adult↗
PubMed2004

Amyotrophic lateral sclerosis: a consensus viewpoint on designing and implementing a clinical trial.

In November 2002, an advisory board meeting was convened by Novartis Pharma to provide recommendations and rationale for clinical trials designed to evaluate new treatments, such as TCH346, for amyotrophic lateral sclerosis (ALS). In terms of selecting appropriate outcome measures, the panel recommended the use of the ALS Functional Rating Scale (ALSFRS-R) to measure primary endpoints. A review of other key issues in this area including regional variations in the epidemiology, diagnosis and management of ALS, defining patient populations and doses of trial medication, and accommodating the likelihood of co-medication with pre-existing treatment in trial design, are discussed.

Amyotrophic Lateral Sclerosis↗
PubMed2004

ALSFRS-R.

The ALSFRS-R is an attractive primary outcome measure in clinical trials of ALS because it is validated, easy to administer, minimizes dropout, reduces cost, and correlates with survival. Unlike the other standard outcome measures currently employed, the ALSFRS-R is also a measure of global function.

Activities of Daily Living↗
PubMed2004

Improving efficiency of ALS clinical trials using lead-in designs.

We describe designs for clinical trials in ALS including two that are more efficient than the standard two-arm, parallel design. The more efficient designs incorporate a lead-in period followed by a randomized intervention (drug or placebo) period. Efficacy of the more efficient designs is based on measuring, within each patient, the difference in slope while on the new treatment compared to the lead-in period. We demonstrate, with sample size calculations, that the lead-in designs are considerably more efficient than the standard two-arm, parallel design. Sample sizes can be reduced by 44% for a 12-month study using ALSFRS rate of decline as a primary endpoint for a two-arm trial with 4 months lead-in compared to a parallel design. A sample size reduction of 70% can be realized with variable lead-in compared to a parallel design.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Drug therapy for amyotrophic lateral sclerosis: Where are we now?

In the 60 years since Lou Gehrig died from amyotrophic lateral sclerosis (ALS) there have been numerous advances in our understanding of this disease. However, scant progress has been made regarding disease-altering treatments. Today most physicians still recommend vitamin E, which is the treatment Gehrig himself received. In this paper we will review what is currently known about the pathophysiology of ALS as well as the history of clinical trials in ALS. We indicate current and future directions in research and clinical trials, and also argue that a logical next step for clinical trials in ALS should be combination drug treatment.

Amyotrophic Lateral Sclerosis↗
PubMed2002

Role of fatigue in limiting physical activities in humans with neuromuscular diseases.

New methods of examining both central and peripheral fatigue are now available. A broader understanding of the mechanisms of fatigue in healthy human subjects has begun to emerge. The mechanisms of fatigue in patients with various neuromuscular diseases are even more complex than in healthy persons. Examples of both central and peripheral fatigue in various neuromuscular diseases and other disorders are presented, including metabolic myopathy, chronic fatigue syndrome, postpolio syndrome, and amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗