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Biomedical subjects

E J Kasarskis

Publications and source records attributed to E J Kasarskis.

At least 19 recordsLinked to original sources
PubMed2006

Enteral tube feeding for amyotrophic lateral sclerosis/motor neuron disease.

BACKGROUND: Enteral feeding (tube feeding) is offered to many people with amyotrophic lateral sclerosis/motor neuron disease experiencing difficulty swallowing (dysphagia) and maintaining adequate nutritional intake leading to weight loss. OBJECTIVES: The aim of this review is to examine the efficacy of percutaneous endoscopic gastrostomy placement or other tube feeding placement on: (1) survival; (2) nutritional status; (3) quality of life. Another aim is to examine the minor and major complications of percutaneous endoscopic gastrostomy. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group Trials Register (June 2005), MEDLINE (from January 1966 to June 2005), and EMBASE (from January 1980 to June 2005) for randomized controlled trials. In addition we searched MEDLINE (January 1966 to June 2005) and EMBASE (January 1980 to June 2005) to identify non-randomized studies that might be worthy of review and discussion. We checked references in published articles, proceedings of scientific meetings, and enlisted personal communications to identify any additional references. SELECTION CRITERIA: All randomized and quasi-randomized controlled trials were to have been selected. Since no such trials were discovered, all prospective and retrospective controlled studies were reviewed in the 'Background' or 'Discussion' sections of the review. DATA COLLECTION AND ANALYSIS: We independently assessed study methodological design and extracted data. We considered the following outcomes: (1) survival rate in months (of primary interest), (2) nutritional status measured by weight change, change in body mass index, or other quantitative index of nutritional status, and (3) self-perceived quality of life We were also interested in reports of safety of the procedure as indicated by (4) minor and major complications of percutaneous endoscopic gastrostomy or other feeding tube placement. MAIN RESULTS: We found no randomized controlled trials comparing the efficacy of enteral tube feeding with those people who continued to eat orally, without enteral feeding. We summarized the results of retrospective and prospective case controlled studies in the 'Discussion' section of this review. AUTHORS' CONCLUSIONS: There are no randomized controlled trials to indicate whether enteral tube feeding is beneficial compared to continuation of oral feeding for survival. The 'best' evidence to date, based on controlled prospective cohort studies, suggests an advantage for survival in all people with amyotrophic lateral sclerosis/motor neuron disease, but these conclusions are tentative. Evidence for improved nutrition is also incomplete but tentatively favorable. Quality of life has only been addressed by a few researchers and needs more serious attention.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Occurrence of amyotrophic lateral sclerosis among Gulf War veterans.

BACKGROUND: In response to Gulf War veterans' concerns of high rates of ALS, this investigation sought to determine if Gulf War veterans have an elevated rate of ALS. METHODS: A nationwide epidemiologic case ascertainment study design was used to ascertain all occurrences of ALS for the 10-year period since August 1990 among active duty military and mobilized Reserves, including National Guard, who served during the Gulf War (August 2, 1990, through July 31, 1991). The diagnosis of ALS was confirmed by medical record review. Risk was assessed by the age-adjusted, average, annual 10-year cumulative incidence rate. RESULTS: Among approximately 2.5 million eligible military personnel, 107 confirmed cases of ALS were identified for an overall occurrence of 0.43 per 100,000 persons per year. A significant elevated risk of ALS occurred among all deployed personnel (RR = 1.92; 95% CL = 1.29, 2.84), deployed active duty military (RR = 2.15, 95% CL = 1.38, 3.36), deployed Air Force (RR = 2.68, 95% CL = 1.24, 5.78), and deployed Army (RR = 2.04; 95% CL = 1.10, 3.77) personnel. Elevated, but nonsignificant, risks were observed for deployed Reserves and National Guard (RR = 2.50; 95% CL = 0.88, 7.07), deployed Navy (RR = 1.48, 95% CL = 0.62, 3.57), and deployed Marine Corps (RR = 1.13; 95% CL = 0.27, 4.79) personnel. Overall, the attributable risk associated with deployment was 18% (95% CL = 4.9%, 29.4%). CONCLUSIONS: Military personnel who were deployed to the Gulf Region during the Gulf War period experienced a greater post-war risk of ALS than those who were not deployed to the Gulf.

Adult↗
PubMed1999

A retrospective study of percutaneous endoscopic gastrostomy in ALS patients during the BDNF and CNTF trials.

Percutaneous endoscopic gastrostomy (PEG) provides a reliable route for nutrition and hydration in ALS patients with dysphagia. We performed a retrospective analysis of the CNTF and BDNF databases to determine the clinical status of ALS patients within 30 days preceding PEG insertion. This analysis revealed an approximately 50% reduction of function across multiple measures of ALS disease status. A trend to earlier intervention with PEG was apparent upon review of published studies and the CNTF and BDNF studies. By comparing the rate of decline pre- and post-PEG, nutritional supplementation via PEG stabilized the weight loss experienced by patients. Death within 30 days post-PEG was associated with a marked reduction in forced vital capacity (FVC) and identified a group of ALS patients in whom PEG should be cautiously performed. These data emphasize the importance of sequential measurement of FVC in managing ALS patients to guide the timing of nutritional intervention with PEG.

Adult↗
PubMed1999

Mutations in the promoter reveal a cause for the reduced expression of the human manganese superoxide dismutase gene in cancer cells.

Manganese superoxide dismutase (MnSOD) has been shown to play an important role in preventing the development of cancer. MnSOD activity is reduced in many transformed cells and tumor tissues. We previously showed that the reduced level of MnSOD activity in cancer cells was not due to a defect in the primary structure of MnSOD protein, but rather was due to defects in gene expression. To elucidate the cause for the reduced expression of human MnSOD in cancer, we investigated the nucleotide sequence in the regulatory region of the MnSOD gene in a normal human cell line and various human tumor cell lines. A DNA fragment spanning 3.4 kb 5' flanking region of the MnSOD gene isolated from a normal human genomic DNA library was used to determine the DNA sequence of MnSOD promoter. PCR primers were used for amplification of the 3.4 kb 5' flanking region of the human MnSOD gene in cancer cells. Sequence analysis identified three heterozygous mutations in the proximal region of the promoter in five human tumor cell lines. These mutations, clustered around the GC-rich region of the human MnSOD promoter, change the binding pattern of AP-2 and lead to a reduction in transcription activity using a luciferase reporter assay system. These results suggest that the reduced level of MnSOD expression in some tumor cells is, at least in part, due to a defect in the DNA sequence of the promoter region.

Base Sequence↗
PubMed1999

An intronic NF-kappaB element is essential for induction of the human manganese superoxide dismutase gene by tumor necrosis factor-alpha and interleukin-1beta.

Tumor necrosis factor-alpha (TNF) and interleukin-1beta (IL-1) are cytokines that induce expression of various genes through activation of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kappaB). We have previously cloned the entire human MnSOD (SOD2) gene and found several NF-kappaB-binding sites in the 5' and 3' flanking and intronic regions. To test whether these putative NF-kappaB-binding sites are able to respond to TNF and IL-1, we performed induction analysis using various deletion constructs ligated to a luciferase reporter gene. We found that the 5' and 3' flanking regions containing several NF-kappaB-binding sites do not mediate MnSOD induction by TNF or IL-1. When a 342-bp intron 2 fragment containing NF-kappaB, C/EBP, and NF-1 binding sites was linked to the basal promoter of the SOD2 gene, transcriptional activities were significantly increased in response to TNF and IL-1 in an orientation- and position-independent manner. To accurately identify the element that is most critical for the enhancer activity, deletions and specific mutations of each individual site were studied. The results indicated that the NF-kappaB binding site is essential but not sufficient for TNF- or IL-1-mediated induction. Furthermore, NF-kappaB elements in the 5' and 3' flanking regions could be made to function in TNF or IL-1 induction when they were transposed to the intronic fragment. Taken together, these results suggest that an NF-kappaB element and its location in the SOD2 gene is critical for TNF/IL-1-mediated induction. However, a complex interaction between NF-kappaB and other transcription elements is needed for a high-level induction.

Base Sequence↗
PubMed1998

Nutritional management in amyotrophic lateral sclerosis: a worldwide perspective.

Although respiratory failure is the primary cause of death in patients with amyotrophic lateral sclerosis (ALS), the management of nutritional status is important to enhancing the quality of life and optimising the timing of interventive techniques. Progressively weakening muscles impair the patient's ability to eat, and nearly all patients with ALS develop severe dysphagia. If nutritional support is not provided, food and fluid consumption may be greatly restricted, leading to weight loss and malnutrition. This may be compounded by impaired respiratory functions, which place increased energy demands on the patient. This paper describes the nutritional needs of ALS patients from a worldwide and cross-cultural perspective. In particular, the differences between a paternalistic and a patient-centred approach to treatment are addressed. The need for further study into the nutritional status of ALS patients and the issue of parenteral and enteral nutritional therapy, particularly percutaneous endoscopic gastrostomy, are discussed.

Amyotrophic Lateral Sclerosis↗
PubMed1997

The use of upper extremity anthropometrics in the clinical assessment of patients with amyotrophic lateral sclerosis.

We evaluated the feasibility of using upper extremity anthropometrics to monitor the clinical status of 18 patients with amyotrophic lateral sclerosis (ALS). The bone-free arm muscle area (AMA) was computed using measurement of triceps skinfold thickness and the mid-upper arm circumference according to published formulae. The AMA correlated significantly with body mass, isokinetic muscle force generation, cross-sectional muscle area on computerized tomography scanning, and pulmonary functions including forced vital capacity and maximal voluntary ventilation. Serial determinations of AMA demonstrated a decline in 10 of 13 patients over 6 months. We pilot tested the use of AMA in a clinical trial of ciliary neurotrophic factor (CNTF) in the treatment of ALS. The AMA progressively decreased by 13%, 15%, and 30% in ALS patients treated with 0 microg CNTF/kg, 15 microg CNTF/kg, and 30/microg CNTF/kg, respectively, over a 9-month treatment period. We conclude that measurement of AMA provides a simple, inexpensive method to monitor the progression of muscle atrophy in ALS patients. The technique does not require effort on the part of the patient and as such, appears to have potential utility as an outcome measure in clinical drug trials.

Adult↗
PubMed1996

Variable phenotype of rapid-onset dystonia-parkinsonism.

Rapid-onset dystonia-parkinsonism (RDP) is an autosomal dominant disorder characterized by the rapid onset of dystonic spasms and parkinsonism over a period of a few hours to weeks after their onset. We have seen two additional members of this previously reported family with RDP who present with a more gradual progression of their disorder over 6-18 months. One of these individuals experienced the rapid progression of symptoms 2 years after an initial stabilization of his condition. The RDP phenotype is variable, and presentation may be gradual in some cases. Cerebrospinal fluid neurotransmitter levels in these two and other family members suggest involvement of the dopaminergic pathways in RDP.

Adolescent↗
PubMed1996

The neuronal voltage-gated sodium channel, Scn8a, is essential for postnatal maturation of spinal, but not oculomotor, motor units.

Mice with a nontargeted transgene insertion at the motor endplate disease (med) locus (med(tg)) contain a deletion of a novel gene encoding a neuronal voltage-gated sodium channel, designated Scn8a. We characterized severe skeletal muscle atrophy beginning by Postnatal Day 10 (P10) and death by P20 in the med(tg) mouse. Denervation was functional, rather than structural, since the Scn8a mutation was not accompanied by retraction of neuromuscular contacts, motoneuron death, or decreased motoneuron soma diameter. Although pathology consistent with denervation was seen in both hindlimb and forelimb musculature, the postnatal maturation of the extraocular muscles was not altered. The onset of paralysis is likely coincident with the time that the Scn8a sodium channel normally assumes a critical role in the initiation and/or propagation of action potentials in spinal motoneurons. By contrast, the lack of consequences for extraocular muscle suggests that the Scn8a voltage-gated sodium channel may be of relatively minor importance for oculomotor motoneurons.

Animals↗
PubMed1996

Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive muscle atrophy and weakness. Although dysphagia is a universal feature of this illness, the nutritional and metabolic status of ALS patients has received little attention. We performed serial measurements of muscle power, body composition, energy expenditure, nitrogen balance, and dietary intake on ALS patients on three occasions over 6 mo in the General Clinical Research Center of the University of Kentucky Medical Center. Data were analyzed in reference to the time of death. Regression analysis demonstrated progressive decreases in body fat, lean body mass, muscle power, and nitrogen balance and an increase in resting energy expenditure as death approached. The changes in body composition were greater in males. Energy and protein consumption averaged 84% and 126% of the recommended dietary allowances, respectively, but did not correlate with complaints of dysphagia. We conclude that ALS patients have a chronically deficient intake of energy and recommended augmentation of energy intake rather than the consumption of high-protein nutritional supplements.

Adult↗
PubMed1995

Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study.

We measured aluminum (Al), calcium (Ca), and iron (Fe) levels in neuronal cytoplasm and nucleus, capillaries, and neuropil in samples of ventral cervical spinal cord from 5 patients with sporadic amyotrophic lateral sclerosis (ALS) and 5 age-matched controls using laser microprobe mass spectrometry (LMMS). The concentration of Al was not altered in any area in the ALS samples. In contrast, Fe and Ca were increased 1.5-2-fold in the nucleus and cytoplasm of ALS neurons but not in capillaries and neuropil. These findings do not support the hypothesis that Al is enriched in spinal cord of sporadic ALS as has been reported for Guamanian ALS/Parkinson's dementia. The elevations of Fe in spinal neurons are consistent with reports of increased Fe in bulk samples of ALS spinal cord. The presence of increased Fe within spinal neurons may be significant in the pathogenesis of motor neuron degeneration by catalyzing the generation of reactive oxygen species within specific cells.

Aged↗
PubMed1995

Neuronal localization of metallothioneins in rat and human spinal cord.

The immunocytochemical localization of the metallothioneins (MT), a family of low molecular weight, heavy metal binding proteins, was investigated in rat and human spinal cord using two distinct antibodies. Polyclonal antibodies were raised to the peptide (SCKCKECKCTS), an epitope common to all human MT isoforms. The monoclonal antibody, E9 which recognizes a different epitope of the MT protein, was also used. Similar results were obtained with either antibody. Both antibodies recognized authentic MT from rabbit liver and horse kidney on Western blots. Immunoreactivity was localized primarily in the cytoplasm of motoneurons in the anterior horn of cervical and lumbar cord. However nuclear staining was present in some motoneurons in both rat and human cord. Intense nuclear, as well as cytoplasmic staining was seen in astrocytes. Capillary endothelia, ependymal cells, arachnoid and pia were also positive for MT.

Amino Acid Sequence↗
PubMed1993

Arsenic poisoning in central Kentucky: a case report.

A recent case of chronic arsenic intoxication due to prolonged accidental ingestion of a commercially available crabgrass killer illustrates one of the more common etiologies of present day arsenic poisoning. A review of 20 years of arsenic poisoning at the University of Kentucky (21 cases) revealed no cases attributable to an industrial source. A tabulation of the 21 most recent cases is included.

Adolescent↗
PubMed1993

Rapid-onset dystonia-parkinsonism.

We studied a large family with a previously undescribed, autosomal dominant dystonia-parkinsonism syndrome. We chose to call the disorder "rapid-onset dystonia-parkinsonism" (RDP) based on the unusually rapid evolution of signs and symptoms. Affected individuals developed dystonia and parkinsonism between 14 and 45 years of age. The onset was acute in six individuals with the abrupt onset of symptoms over the course of several hours, and subacute in four others who had evolution over several days or weeks. Thereafter, progression of symptoms was usually very slow. Two had intermittent focal dystonia without parkinsonism, and one obligate gene carrier was asymptomatic at 68 years. CSF levels of homovanillic acid were decreased in the two individuals tested, but dopaminergic therapy provided only slight benefit. The DYT1 gene responsible for early-onset, generalized idiopathic torsion dystonia in Jewish and some non-Jewish families has been mapped to chromosome 9q34. Linkage analysis with three markers near the DYT1 gene showed several obligate recombinations, excluding DYT1 as a candidate gene for RDP. We believe RDP is unique and should be classified separately from other forms of hereditary dystonia-parkinsonism.

Adolescent↗