Biomedical subjects

Zachary Simmons

Publications and source records attributed to Zachary Simmons.

13 recordsLinked to original sources

PubMed2006

A rapid screening battery to identify frontal dysfunction in patients with ALS.

We studied the relationship between verbal associative fluency, verbal abstract reasoning, and judgment in ALS using a 20-minute screening evaluation. Deficiencies in these measures were found in 20.0%, 18.6%, and 35.7% of patients with limb-onset ALS and in 37.5%, 25.0%, and 60.0% of patients with bulbar-onset ALS. This simple screen identifies deficits that affect discussions of treatment interventions and end-of-life issues.

Adult↗

PubMed2006

Genetic risk factors associated with lipid-lowering drug-induced myopathies.

Lipid-lowering drugs produce myopathic side effects in up to 7% of treated patients, with severe rhabdomyolysis occurring in as many as 0.5%. Underlying metabolic muscle diseases have not been evaluated extensively. In a cross-sectional study of 136 patients with drug-induced myopathies, we report a higher prevalence of underlying metabolic muscle diseases than expected in the general population. Control groups included 116 patients on therapy with no myopathic symptoms, 100 asymptomatic individuals from the general population never exposed to statins, and 106 patients with non-statin-induced myopathies. Of 110 patients who underwent mutation testing, 10% were heterozygous or homozygous for mutations causing three metabolic myopathies, compared to 3% testing positive among asymptomatic patients on therapy (P = 0.04). The actual number of mutant alleles found in the test group patients was increased fourfold over the control group (P < 0.0001) due to an increased presence of mutation homozygotes. The number of carriers for carnitine palmitoyltransferase II deficiency and for McArdle disease was increased 13- and 20-fold, respectively, over expected general population frequencies. Homozygotes for myoadenylate deaminase deficiency were increased 3.25-fold with no increase in carrier status. In 52% of muscle biopsies from patients, significant biochemical abnormalities were found in mitochondrial or fatty acid metabolism, with 31% having multiple defects. Variable persistent symptoms occurred in 68% of patients despite cessation of therapy. The effect of statins on energy metabolism combined with a genetic susceptibility to triggering of muscle symptoms may account for myopathic outcomes in certain high-risk groups.

AMP Deaminase↗

PubMed2006

A clinical pilot study: high frequency chest wall oscillation airway clearance in patients with amyotrophic lateral sclerosis.

Respiratory complications are common in patients with amyotrophic lateral sclerosis (ALS) with respiratory failure representing the most common cause of death. Ineffective airway clearance resultant from deficient cough frequently contributes to these abnormalities. We sought to evaluate the effectiveness of high frequency chest wall oscillation (HFCWO) administered through the Vest Airway Clearance System when added to standard care in preventing pulmonary complications and prolonging the time to death in patients with ALS. This is a single center study performed at the Penn State Milton S. Hershey Medical Center (HMC). Nine patients with a diagnosis of ALS and concurrently receiving non-invasive ventilatory support with bi-level positive airway pressure (BiPAP) were recruited from the outpatient clinic at HMC. Four patients were randomized to receive standard care and five patients to receive standard care plus the addition of HFCWO administered twice-daily for 15 min duration. Longitudinal assessments of oxyhemoglobin saturation, forced vital capacity (FVC), and adverse events were obtained until time of death. Pulmonary complications of atelectasis, pneumonia, hospitalization for a respiratory-related abnormality, and tracheostomy with mechanical ventilation were monitored throughout the study duration. No differences were observed between treatment groups in relation to the rate of decline in FVC. The addition of HFCWO airway clearance failed to improve time to death compared to standard treatment alone (340 days +/- 247 vs. 470 days +/- 241; p = 0.26). The random allocation of HFCWO airway clearance to patients with ALS concomitantly receiving BiPAP failed to attain any significant clinical benefits in relation to either loss of lung function or mortality. This study does not exclude the potential benefit of HFCWO in select patients with ALS who have coexistent pulmonary diseases, pre-existent mucus-related pulmonary complications, or less severe levels of respiratory muscle weakness.

Adult↗

PubMed2006

Differential expression of genes in amyotrophic lateral sclerosis revealed by profiling the post mortem cortex.

The possible causes of ALS are unknown and multiple biological systems have been implicated. The goal of this study was to use gene expression profiling to evaluate a broad spectrum of systems in ALS. For this study, the medial lip of the human motor cortex and adjacent sensory cortex were collected at autopsy from five ALS patients and three normal individuals. Quantitative filter analysis revealed differential expression of mRNAs normalized to internal standards. A significant difference in expression of 275 genes was found in the ALS motor cortex; of the genes whose expression was changed, 10 were up-regulated and 265 were down-regulated. Six of the up-regulated genes were associated with cell surface activity and two were glutamate receptors; the latter is potentially consistent with the idea of excitotoxicity contributing to neurodegeneration in ALS. Of the down-regulated genes, the largest number were associated with transcription followed by those involved in antioxidant systems, inflammation, regulation of motor neuron function, lipid metabolism, protease inhibition, and protection against apoptosis including vascular endothelial growth factor. There were no significant differences in gene expression patterns between the sensory and motor cortex in the ALS brains. A total of 10% of the genes identified by microarray were chosen from each of the gene groups for validation by quantitative real time PCR (QRT-PCR). In order to increase the reliability of our gene array data, newly acquired motor and sensory cortex of ALS and control cases (n = 4 each) were used for validation. Of these, 86.4% changed in the same direction as determined in the microarrays. The gene profile data reported here are consistent with evidence that the ALS brain is characterized by an environment that is permissive for apoptosis, excitotoxicity and abnormal ubiquitination. This gene array study also suggested that a metal imbalance particularly for zinc could exist in ALS. Finally, given the amount of cellular stress that is thought to be part of the pathogenesis in ALS, there was a notable lack of increase in genes required to mount a protective response. This latter observation provides a conceptual framework in which to consider the possibility that ALS could result from a failure to mount adequate protective responses to physiological insults that, left unchecked, could progress to neurodegeneration.

Aged↗

PubMed2005

Familial clustering of muscular and cardiac involvement in myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is associated with both skeletal and cardiac muscle involvement. The aim of the present study was to determine whether familial clustering is observed in the severity of muscle involvement in DM1. We evaluated 51 sibling groups constituting 112 patients with genetically-verified DM1. The siblings were similar to each other in age, cytosine-thymine-guanine (CTG) repeat length, age at disease onset, muscular impairment rating score, and electrocardiographic markers of cardiac conduction disease. After adjusting for the similarities between siblings in age and CTG repeat length, the siblings remained similar to each other in measures of both skeletal and cardiac muscle involvement. These results suggest that factors other than CTG repeat length play a role in the severity and progression of the degenerative skeletal and cardiac muscle disease in DM1.

Adolescent↗

PubMed2005

Management strategies for patients with amyotrophic lateral sclerosis from diagnosis through death.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disorder that is inevitably fatal. There are no effective treatments to stop or reverse the natural course of the disease. The role of the physician is to provide comfort and optimize quality of life. REVIEW SUMMARY: Management of patients with ALS is a process extending over months to years. It begins with breaking the news of the diagnosis and extends through the terminal phase. Medication may extend lifespan by a small amount. However, most efforts are centered around symptom management. Areas of importance include respiration, nutrition, secretions, communication, pseudobulbar affect, therapy and exercise, spasticity and cramps, pain, depression and suicide, spirituality and religion, cognitive changes, the development of advance directives, and care at the end of life. Multidisciplinary ALS clinics provide much-needed support for patients with ALS and their caregivers. CONCLUSION: Although physicians cannot cure ALS or even halt progression, there is much that can be done to manage the physical and emotional symptoms, thereby maintaining or enhancing quality of life.

Amyotrophic Lateral Sclerosis↗

PubMed2004

Increased incidence of the Hfe mutation in amyotrophic lateral sclerosis and related cellular consequences.

The etiology of amyotrophic lateral sclerosis (ALS) is unknown. The presence of mutations in the superoxide dismutase gene (SOD1) has led to theories regarding a role for oxidative stress in the pathogenesis of this disease. A primary cause of oxidative stress is perturbations in cellular iron homeostasis. Cellular iron mismanagement and oxidative stress are associated with a number of neurodegenerative diseases. One mechanism by which cells fail to properly regulate their iron status is through a mutation in the Hfe gene. Mutations in the Hfe gene are associated with the iron overload disease, hemochromatosis. In the current study, 31% of patients with sporadic ALS carried a mutation in the Hfe gene, compared to only 14% of patients without identifiable neuromuscular disease, or with neuromuscular diseases other than ALS (p<0.005). To determine the cellular consequences of carrying an Hfe mutation, a human neuronal cell line was transfected with genes carrying the Hfe mutation. The presence of the Hfe mutation disrupted expression of tubulin and actin at the protein levels potentially consistent with the disruption of axonal transport seen in ALS and was also associated with a decrease in CuZnSOD1 expression. These data provide compelling evidence for a role for the Hfe mutation in etiopathogenesis of ALS and warrant further investigation.

Age of Onset↗

PubMed2004

The development of risk assessment models for carpal tunnel syndrome: a case-referent study.

The present study developed risk assessment models for carpal tunnel syndrome (CTS) which can provide information of the likelihood of developing CTS for an individual having certain personal characteristics and occupational risks. A case-referent study was conducted consisting of two case groups and one referent group: (1) 22 work-related CTS patients (W-CTS), (2) 25 non-work related CTS patients (NW-CTS), and (3) 50 healthy workers (HEALTHY) having had no CTS history. The classification of CTS patients into one of the case groups was determined according to the type of insurance covering their medical costs. Personal characteristics, psychosocial stresses at work, and physical work conditions were surveyed by using a questionnaire tailor-designed to CTS (reliability of each scale > or = 0.7). By contrasting the risk information of each case group to that of the referent group, three logistic regression models were developed: W-CTS/HEALTHY, NW-CTS/HEALTHY, and C-CTS/HEALTHY (C-CTS, the combined group of W-CTS and NW-CTS). ROC analysis indicated that the models have satisfactory discriminability (d' = 1.91 to 2.51) and high classification accuracy (overall accuracy = 83-89%). Both W-CTS/HEALTHY and C-CTS/HEALTHY include personal and physical factors, while NW-CTS/HEALTHY involves only personal factors. This suggests that the injury causation of NW-CTS patients should be attributable mainly to their 'high' personal susceptibility to the disorder rather than exposure to adverse work conditions, while that of W-CTS patients be attributable to improper work conditions and CTS-prone personal characteristics in combination.

Carpal Tunnel Syndrome↗

PubMed2004

Factors supporting quality of life over time for individuals with amyotrophic lateral sclerosis: the role of positive self-perception and religiosity.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neuromuscular disease with no known cure. Maintaining quality of life (QOL) as the disease progresses is an important treatment goal. PURPOSE: the purpose of this study is to identify factors that support QOL as ALS progresses. METHODS: Changes in QOL were monitored in 162 individuals with ALS at 3- to 4-month intervals. Forty-nine of the participants survived in the study for over 1 year and were included in a longitudinal comparison. The 49 long-term participants were younger and stronger at Time 1 than were the participants who died before reaching the 1-year point. The McGill Quality of Life Scale demonstrated a high and stable QOL despite physical deterioration. RESULTS: Patients maintained a positive self-perception of their health despite the physical deterioration. Over time, self-perception of health and religiosity were shown to be significantly correlated with QOL. CONCLUSIONS: Results support the need for better instrumentation to enable future studies to more precisely measure multiple dimensions of ALS-related QOL, to identify reference points for self-ratings of both health and QOL, and to capture the religious and spiritual mechanisms related to QOL as individuals face the end of life.

Adult↗

PubMed2003

Religiousness is related to quality of life in patients with ALS.

The authors studied quality of life (QOL) and religiousness in 49 patients with ALS over five consecutive visits spanning approximately 1 year. QOL was not significantly correlated with religiousness at entry. Over time, a significant relationship developed between QOL and total, public, and private religiousness.

Adult↗

PubMed2003

Muscle biopsy in the evaluation of patients with modestly elevated creatine kinase levels.

The utility of muscle biopsy in patients with modest elevations of serum creatine kinase (CK) level but normal neurological examinations and nondiagnostic electrodiagnostic studies is uncertain. We performed systematic, extensive studies on muscle biopsies of 20 such patients. A definitive diagnosis was arrived at in only 1 by histochemical studies, although 4 others demonstrated minor myopathic changes. Biochemical evaluation led to a diagnosis in an additional 5. Muscle biopsy is useful for evaluating such patients, but extensive studies of the muscle are necessary.

AMP Deaminase↗

PubMed2002

Hypothyroid myopathy with a strikingly elevated serum creatine kinase level.

Although serum creatine kinase (CK) levels are frequently modestly elevated in patients with hypothyroid myopathy, elevations in serum CK to the levels usually seen in inflammatory myopathies or dystrophies are rare. We report a patient with progressive proximal weakness and a serum CK level of over 29,000 IU/L, in whom subsequent laboratory evaluation identified profound hypothyroidism. Thyroid hormone replacement therapy resulted in resolution of clinical symptoms and a marked reduction in the serum CK level. Such a high serum CK level in a patient with hypothyroidism underscores the importance of assessing thyroid function in patients with weakness, regardless of serum CK levels, even when systemic symptoms and signs of hypothyroidism are minimal or absent.

Adult↗

PubMed2002

Update on diabetic neuropathy.

PURPOSE OF REVIEW: This review will focus on recent advances in the field of diabetic neuropathy, with an emphasis on distal symmetric sensory and sensorimotor polyneuropathy. Some new information in the areas of diabetic amyotrophy and diabetic autonomic neuropathy will also be reviewed. RECENT FINDINGS: The pathogenesis of diabetic neuropathy is multifactorial. There is increasing evidence to link abnormalities in the polyol pathway to the pathogenesis of diabetic neuropathy. In addition, there appear to be abnormalities of nerve regeneration and of sodium and calcium channels. Aldose reductase inhibitors have shown promise in animal models for reversing neuropathy if started early and used for a sufficient time, but those used to date in human trials are probably not of sufficient potency. Neurotrophic factors and vascular endothelial growth factor both also show promise. Specific recommendations and pathways for diabetic foot care have been devised. Lamotrigine and bupropion represent new treatments for neuropathic pain. The role of impaired glucose tolerance is being explored as it relates to polyneuropathy. SUMMARY: An increasing understanding of the pathogenetic mechanisms holds out promise for the effective treatment of diabetic neuropathy. The early detection of abnormal glucose metabolism is particularly important, as treatments will probably be most effective if administered early in the course of the neuropathy, when abnormalities of peripheral nerves are more likely to be reversible.

Diabetic Foot↗