Emergency department observation unit funding.
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Emergency Service, Hospital↗
Biomedical subjects
M A Ross
Publications and source records attributed to M A Ross.
Early region 1 transforming functions are dispensable for mammary tumorigenesis by human adenovirus type 9.
Some human adenoviruses are tumorigenic in rodents. Subgroup A and B human adenoviruses generally induce sarcomas in both male and female animals, and the gene products encoded within viral early region 1 (E1 region) are both necessary and sufficient for this tumorigenicity. In contrast, subgroup D human adenovirus type 9 (Ad9) induces estrogen-dependent mammary tumors in female rats and requires the E4 region-encoded ORF1 oncoprotein for its tumorigenicity. Considering the established importance of the viral E1 region for tumorigenesis by adenoviruses, we investigated whether this viral transcription unit is also necessary for Ad9 to generate mammary tumors. The nucleotide sequence of the Ad9 E1 region indicated that the gene organization and predicted E1A and E1B polypeptides of Ad9 are closely related to those of other human adenovirus E1 regions. In addition, an Ad9 E1 region plasmid demonstrated focus-forming activity in both low-passage-number and established rat embryo fibroblasts, whereas a large deletion within either the E1A or E1B gene of this plasmid diminished transforming activity. Surprisingly, we found that introducing the same transformation-inactivating E1A and E1B deletions into Ad9 results in mutant viruses that retain the ability to elicit mammary tumors in rats. These results are novel in showing that Ad9 represents a unique oncogenic adenovirus in which the E4 region, rather than the E1 region, encodes the major oncogenic determinant in the rat.
Adenovirus E1 Proteins↗
[Effects of vitamins E, C and beta-carotene on DNA damage].
OBJECTIVE: To investigate their effects on lymphocyte damage with supplementation of high-dose vitamins E, C and beta-carotene. METHODS: Healthy men aged 50 - 59 years were selected and randomized into the trial and control groups with 50 in each one. In the trial group, 25 mg of beta-carotene, 100 mg vitamin C and 280 mg vitamin E were given to each subject every day for 20 weeks. Whole blood was collected in both the trial and control groups and its lymphocytes separated. Damage to DNA was analyzed with a"comet" electrophoresis technique, and serum levels of vitamin C, beta-carotene and alpha-tocopherol were determined by high performance liquid chromatography. RESULTS: There was no significant difference in the proportions of spontaneous damage to DNA in lymphocytes between the trial and control groups (6.1% vs. 6.8%). But, proportions of damage to DNA in peripheral lymphocytes increased to 36.14%, 59.45, and 69.62%, respectively, after treatment with 30 micromol/L, 100 micromol/L and 300 micromol/L of H(2)O(2). CONCLUSION: Supplementation of vitamin E, C and beta-carotene could effectively reduce the damage to DNA caused by H(2)O(2).
Antioxidants↗
Analysis of health-related quality of life and muscle impairment in individuals with amyotrophic lateral sclerosis using the medical outcome survey and the Tufts Quantitative Neuromuscular Exam.
OBJECTIVE: The Tufts Quantitative Neuromuscular Exam (TQNE) is commonly used to assess the rate of disease progression in individuals with amyotrophic lateral sclerosis (ALS). The Medical Outcome Study Short Form (SF-36) is a general method to assess health-related quality of life (HRQL). This study examined the relationship between the TQNE and SF-36, established the reliability and responsiveness of each, and contrasted the HRQL between individuals with ALS and the general population. DESIGN: Subjects (31) completed the SF-36 and TQNE within 1 week to determine reliability. Subjects (17) also completed both the TQNE and SF-36 each month for 1 year after diagnosis of ALS to establish the relationship between the two assessment tools. SETTING: A primary care university teaching hospital. PATIENTS: Thirty-one subjects with an age range of 27 to 76 years (mean 59.1, SD 10.32), recently diagnosed with ALS. RESULTS: Each test was highly reliable and responsive. The intraclass correlations (2, 1) were consistently higher for the TQNE (.93 to .98) than for the SF-36 (.57 to .90). Changes in physical function were correlated to changes in lower extremity force megascores (.48). CONCLUSION: Both the TQNE and the SF-36 are reliable and responsive and appear important in characterization of patient status after ALS is diagnosed.
Activities of Daily Living↗
Toward earlier diagnosis of amyotrophic lateral sclerosis: revised criteria. rhCNTF ALS Study Group.
We modified the World Federation of Neurology (WFN) diagnostic criteria for ALS to facilitate early diagnosis and used these criteria for enrollment of ALS patients in a clinical trial. The criteria developed required lower motor neuron (LMN) involvement in at least two limbs and upper motor neuron involvement in at least one region (bulbar, cervical, or lumbosacral). The EMG finding of fibrillation potentials was required for evidence of LMN involvement. Electrodiagnostic studies, neuroimaging, and laboratory studies were also used to exclude disorders that might mimic ALS. Using these criteria, the diagnosis of ALS was made at a mean time of 9.7 months from onset of symptoms, which compares favorably with the 12-month period cited in the literature. Using clinical assessment at completion of the trial, the diagnosis of ALS was believed to be accurate in those patients entered in the trial. However, pathologic confirmation of the diagnosis of ALS was not obtained. Based on our preliminary experience, we propose that these ALS diagnostic criteria will facilitate early diagnosis of ALS. Future studies should prospectively compare these criteria with the WFN criteria currently in use.
Amyotrophic Lateral Sclerosis↗
Patient confidentiality and the law.
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Canada↗
Impact on the care of the emergency department chest pain patient from the chest pain evaluation registry (CHEPER) study.
This study examines the question of whether chest pain observation units increase the proportion of chest pain patients with an extended evaluation for cardiac ischemia ("rule out myocardial infarction [MI] evaluation"), decrease the number of missed MIs, and decrease costs. This is a multiple site registry study of 8 established chest pain observation units (complying with the American College Emergency Physician's Observation Section's standards) compared with previous studies on chest pain evaluation without the use of observation (5 studies, 12,405 patients). A total of 23,407 of 444,189 emergency department patients (5.3%) had the chief complaint of chest pain during the study period. In the chest pain observation units, 153 of 2,229 patients (6.9%) with acute MI were identified. Most of the observation chest pain patients (76%) were discharged home without hospital admission. Compared to previous studies, a higher proportion of patients underwent a "rule out MI evaluation" (67%, 95% confidence interval [CI] 66%, 68% vs 57%, 95% CI 56%, 58%; p <0.001) equal to 2,250 additional patients completely evaluated ($1,219,500 additional costs). A lower proportion of MIs were missed (0.4%, 95% CI 0.3%, 0.5% vs 4.5%, 95% CI 4.0% to 5.5%; p <0.001) as estimated by return visits within 72 hours. Compared to previous studies, final hospital admission rate was lower (47%, 95% CI 46%, 48% vs 57%, 95% CI 56%, 58%; p <0.001), equal to 2,314 hospital admissions avoided in the study population ($4,093,466 saved costs). Calculated true costs overall were lower by $2,873,966 at the study hospitals. Thus, chest pain observation units increased the proportion of chest pain patients thoroughly evaluated with improved quality of care and lower costs.
Chest Pain↗
Reliability of maximal voluntary isometric contraction testing in a multicenter study of patients with amyotrophic lateral sclerosis. Syntex/Synergen Neuroscience Joint Venture rhCNTF ALS Study Group.
Maximal voluntary isometric contraction (MVIC) is becoming widely used for monitoring disease progression in amyotrophic lateral sclerosis (ALS). We evaluated the variability of MVIC in a large multicenter (29 sites) drug trial in ALS. Intra- and interrater variability were assessed twice during the 19-month study. Intrarater reliability increased from the first to the second test, approaching the reliability reported for a single experienced clinical evaluator, but interrater reliability did not. Multiple clinical evaluators in a single site increased the variability of MVIC measurements. Rigorous quality assurance standards and monitoring of clinical evaluators should be incorporated into the design of multicenter studies using MVIC, since low variability is necessary to detect a modest treatment effect.
Adult↗
A brief quality-of-life measure for ALS clinical trials based on a subset of items from the sickness impact profile. The Syntex-Synergen ALS/CNTF Study Group.
We previously demonstrated a significant relationship (P<0.0001) between maximum voluntary isometric contraction (MVC) plus pulmonary function scores (the Tufts Quantitative Neuromuscular Exam Combination Megascore (TQNE CM)), and the Sickness Impact Profile (SIP) in a cohort of 524 ALS patients. Because the 136-item SIP questionnaire can be difficult to administer in this population, we examined SIP subscales and clinically derived item sets in relation to the TQNE CM in an effort to define a briefer measure of quality of life for use in clinical trials. Two 'Mini-SIP' indices performed as well as the overall SIP in reflecting the impact of muscle weakness on ALS patients' quality of life: a combination of two SIP subscales ('SIP-33'), and a 19-item set of questions independently chosen by a panel of ALS specialists ('SIP/ALS-19'). Either index potentially could be useful in ALS clinical trials. The SIP/ALS-19 is currently being used in a National ALS data base, providing an opportunity to evaluate its utility prospectively against other QOL measures in ALS patients.
Amyotrophic Lateral Sclerosis↗
Acquired motor neuron disorders.
The acquired motor neuron disorders are a heterogeneous group of conditions in which motor neuron degeneration or dysfunction produces the predominant manifestation of weakness, while the sensory system is clinically spared. The disorders most commonly seen in clinical practice are amyotrophic lateral sclerosis, late manifestations of poliomyelitis, and lower motor neuron syndromes, including motor neuropathy. Less often, acquired motor neuron disorders may complicate metabolic, toxic, or systemic disorders. The pathogenesis of most acquired motor neuron disorders is poorly understood, and treatment is mainly supportive; however clues to understanding the pathogenesis of amyotrophic lateral sclerosis are emerging, and new pharmacologic therapies are available. There is a growing sense of hope that combinations of drugs that are currently being tested may impact the survival of amyotrophic lateral sclerosis.
Amyotrophic Lateral Sclerosis↗
Antioxidant supplementation decreases oxidative DNA damage in human lymphocytes.
The association between high intake of fruit and vegetables and low incidence of certain cancers is well established. Dietary antioxidants present in these foods are thought to decrease free radical attack on DNA and hence to protect against mutations that cause cancer, but this causal mechanism remains conjectural. We have adopted a molecular epidemiological approach to this question, based on a modified alkaline single-cell gel electrophoresis assay ("comet assay") which specifically detects oxidation of pyrimidines in the DNA of human lymphocytes. In a survey of men 50-59 years of age living in the northeast of Scotland, smokers initially showed significantly more base damage than nonsmokers. Correlations between oxidative base damage and plasma concentrations of various antioxidants were generally negative but not statistically significant. Supplementation of the diet for 20 weeks with vitamin C (100 mg/day), vitamin E (280 mg/day), and beta-carotene (25 mg/day) resulted in a highly significant (P < 0.002) decrease in endogenous oxidative base damage in the lymphocyte DNA of both smokers and nonsmokers. In addition, lymphocytes of antioxidant-supplemented subjects showed an increased resistance to oxidative damage when challenged in vitro with H2O2. These findings strongly support the hypothesis that fruit and vegetables exert a cancer-protective effect via a decrease in oxidative damage to DNA.
Antioxidants↗
Mononeuropathy multiplex associated with celiac sprue.
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Celiac Disease↗
A Dejerine-Sottas neuropathy family with a gene mapped on chromosome 8.
The Patient is a 55-year-old black male who belongs to a large family with 9 affected relatives with autosomal dominant Dejerine-Sottas neuropathy (DSN). Onset of his condition was at 2 years of age with steppage gait followed by severe progressive weakness, atrophy, and sensory loss of his legs and hands accompanied by areflexia and thoracolumbar kyphoscoliosis. The patient became wheelchair confined at age 38. At around age 42, the left shoulder became dislocated and the humeral head underwent aseptic necrosis (Charcot joint). Nerve conduction studies showed absent motor and sensory responses for all major nerves tested. Genetic linkage suggested mapping of this DSN gene on chromosome 8qter. A younger brother with similar neurological findings also demonstrated Charcot joints with bone destruction of the joints of the fourth and fifth fingers.
Chromosome Mapping↗
A placebo-controlled trial of recombinant human ciliary neurotrophic (rhCNTF) factor in amyotrophic lateral sclerosis. rhCNTF ALS Study Group.
Preclinical investigations indicated that recombinant human ciliary neurotrophic factor (rhCNTF) may have potential as therapy for amyotrophic lateral sclerosis (ALS). We evaluated the safety and efficacy of rhCNTF in a prospective, double-blind, placebo-controlled trial in 570 patients with ALS. Patients were randomized to receive 0.5, 2, or 5 micrograms/kg/day rhCNTF, or placebo, for 6 months. The primary efficacy end point was the change from baseline to the last on-treatment value of a combination megascore for limb strength (maximum voluntary isometric contraction) and pulmonary function. Secondary end points included individual arm and leg megascores, pulmonary function tests, an activities-of-daily-living outcome measure, and survival. The four treatment groups were similar at baseline with respect to age, sex, disease duration, and muscle strength values. At all doses tested, rhCNTF had no beneficial effect on the primary or secondary end points. Certain adverse events, as follows, appeared to be dose related: injection site reactions, cough, asthenia, nausea, anorexia, weight loss, and increased salivation. There was an increased number of deaths at the highest dose level. rhCNTF had no beneficial effect on any measure of ALS progression. There were increased adverse events in the 5 micrograms/kg group and increased deaths.
Adult↗
Carpal tunnel release with and without epineurotomy: a comparative prospective trial.
A prospective, comparative study of epineurotomy as an adjunctive procedure to transverse carpal ligament release for the treatment of carpal tunnel syndrome was conducted. Eighty-six patients with 117 involved hands were entered into the study. After entry, all patients completed an extensive preoperative questionnaire, a detailed physical examination, and preoperative neurophysiologic testing. Seventy-five hands were followed for a minimum of 24 months. The operative findings were similar between the group of those undergoing epineurotomy and the group that did not undergo epineurotomy. Postoperatively the twopoint discrimination values for all fingers averaged 5.3 mm and 5.15 mm, respectively, for the epineurotomy and nonepineurotomy groups. The physical findings, neurophysiologic findings, and patient perceptions of outcome after surgery were similar. It was concluded that the study data do not support the use of epineurotomy as an adjunctive procedure during carpal tunnel release.
Adult↗
Placebo-controlled trial of gabapentin in patients with amyotrophic lateral sclerosis. WALS Study Group. Western Amyotrophic Lateral Sclerosis Study Group.
We designed a phase II trial to evaluate the efficacy of gabapentin in slowing the rate of decline in muscle strength of patients with amyotrophic lateral sclerosis (ALS) and to assess safety and tolerability. Gabapentin (800 mg) or placebo was administered t.i.d. in a randomized, double-blinded, placebo-controlled, trial for 6 months. We enrolled 152 patients at eight sites in the United States. The primary outcome measure was the slope of the arm megascore, the average maximum voluntary isometric strength from eight arm muscles standardized against a reference ALS population. A secondary outcome measure was forced vital capacity. Slopes of arm megascores for patients on gabapentin were compared with slopes of those taking placebo using a two-way ANOVA. We observed a nonstatistically significant trend (p = 0.057-0.08) toward slower decline of arm strength in patients taking gabapentin compared with those taking placebo (mean difference 24%, median 37%). We observed no treatment effect on forced vital capacity. Gabapentin was well tolerated by patients with ALS. These results suggest that further studies of gabapentin in ALS are warranted.
Acetates↗
AAEM case report #2: the carpal tunnel syndrome.
The symptoms and signs which constitute the carpal tunnel syndrome (CTS) result from entrapment or compression of the median nerve within the carpal tunnel. Electrodiagnostic studies may objectively document the presence of median neuropathy within the carpal tunnel and help distinguish CTS from other disorders such as cervical radiculopathy, neurogenic thoracic outlet syndrome, proximal median nerve compression syndromes, and polyneuropathy which may either mimic or occasionally coexist with CTS. Recording median nerve responses with wrist and palm stimulation allows determination of the wrist segment conduction velocity which is a more sensitive nerve conduction parameter than wrist latency measurements. Electrodiagnostic testing permits estimation of severity and relative contribution of axonal versus demyelinative nerve injury. This information can provide prognostic information and help guide therapeutic decisions.
Action Potentials↗
The edge of chaos: caring and the bottom line.
Nurse managers need to provide quality health care within a framework of human caring with limited economic resources. Seeking only "bottom line" solutions would seriously affect the well-being of nurses and clients. On the other hand, seeking only human caring solutions would seriously influence the well-being of health care organizations. A composite model balances economics or the "bottom line" and human caring.
Empathy↗