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Biomedical subjects

M A Ross

Publications and source records attributed to M A Ross.

At least 19 recordsLinked to original sources
PubMed2004

Antioxidant treatment for amyotrophic lateral sclerosis / motor neuron disease.

BACKGROUND: Free radical accumulation and oxidative stress have been proposed as contributing to the progression of amyotrophic lateral sclerosis (or motor neuron disease). A range of antioxidant medications are available, and have been studied. OBJECTIVES: To examine the effects of antioxidant medication in the treatment of people with amyotrophic lateral sclerosis. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (July 2003), MEDLINE (from January 1966 to July 2003), EMBASE (from January 1980 to July 2003) and other sources. SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of antioxidant treatment for amyotrophic lateral sclerosis. DATA COLLECTION AND ANALYSIS: The reviewers independently applied the selection criteria, assessed study quality and two reviewers performed independent data extraction. MAIN RESULTS: The search identified 21 studies for consideration but only eight studies met the inclusion criteria. Only two studies used our predetermined primary outcome measure, (survival at 12 months treatment). Sufficient data were available from three studies to allow analysis of the primary outcome measure, and a meta-analysis was performed. In the individual studies no significant effect was observed of vitamin E 500 mg twice daily; acetylcysteine 50 mg/kg daily subcutaneous infusion; or a combination of L-methionine 2 g, vitamin E 400 International Units, and selenium 3 x 10-5g three times daily (Alsemet). No significant effect on the primary outcome measure was observed in a meta-analysis of antioxidants in general when combining the results. No significant differences were demonstrated in secondary outcome measures. REVIEWERS' CONCLUSIONS: There is insufficient evidence of efficacy of individual antioxidants, or antioxidants in general, in the treatment of people with amyotrophic lateral sclerosis. One study reported a mild positive effect, but this was not supported by the analysis we used. Generally the studies were poorly designed, and underpowered, with low numbers of participants and of short duration. Further well-designed trials of medications such as vitamin C and E are unlikely to be performed. If future trials of antioxidant medications are performed, careful attention should be given to sample size, outcome measures, and duration of the trial. The high tolerance and safety, and relatively low cost of vitamins C and E, and other considerations related to the lack of other effective treatments for amyotrophic lateral sclerosis, explain the continuing use of these vitamins by physicians and patients. While there is no substantial clinical trial evidence to support their clinical use, there is no clear contraindication.

Amyotrophic Lateral Sclerosis↗
PubMed2003

Omega-3 and omega-6 fatty acid concentrations in red blood cell membranes relate to schizotypal traits in healthy adults.

Reduced omega-3 and omega-6 fatty acids in red blood cell (RBC) membranes are often found in patients with schizophrenia. Here we investigated whether membrane concentrations of these fatty acids might vary as a function of schizotypal traits in non-psychotic individuals. Twenty-five healthy adults completed the O-LIFE schizotypal trait inventory and fatty acid composition of their venous blood samples was analysed via gas-liquid chromatography. Correlations between schizotypy measures and RBC fatty acids were examined and comparisons made between groups high and low on fatty acid measures and schizotypy scores. The omega-6 fatty acids arachidonic, adrenic and docosapentaenoic acid were directly related to positive schizotypal trait measures, as were most omega-3 fatty acids, but none were related to a negative, withdrawn form of schizotypy. Our findings of high RBC concentrations of omega-3 and omega-6 fatty acids in healthy adults with positive schizotypal traits clearly contrast with the low levels often found in schizophrenia, but are quite consistent with evidence that omega-3 fatty acids (notably EPA) can be useful in the treatment of schizophrenic illness.

Adolescent↗
PubMed2003

Can we eliminate placebo in ALS clinical trials?

BACKGROUND: Previous studies concluded that the decline in strength in patients with amyotrophic lateral sclerosis (ALS) is a linear function. If so, a patient's natural history might serve as the control, instead of placebo, in a clinical trial. METHODS: A placebo-controlled ALS clinical trial included a natural history phase, followed by a 6-month treatment phase. Each patient's forced vital capacity (FVC) score and maximal voluntary isometric contraction (MVIC) raw scores were measured monthly, standardized, and averaged into megascores. For 138 patients, the arm, leg, FVC, arm+leg combination, and arm+leg+FVC combination megascore slopes during the natural history phase and during the placebo phase were compared. RESULTS: The mean slope of megascores during the natural history phase and the mean slope during the placebo phase were not different for the arm, leg, and arm+leg megascores, but were different for the FVC and arm+leg+FVC combination megascores. CONCLUSIONS: Natural history controls may be useful in ALS exploratory trials that use arm megascore slope as the primary outcome measure. However, there are distinct limitations to the use of natural history controls, so that Phase 3 ALS clinical trials require placebo controls.

Amyotrophic Lateral Sclerosis↗
PubMed2001

Principles of observation medicine.

The defining characteristic of emergency medicine is "time," or the acuity of disease presentation. Observation, like resuscitation, involves the management of time-sensitive conditions. In the ED there is a continuum of time-sensitive conditions. This continuum extends from resuscitation on one end to observation on the other. When performed well, observation services have been shown to improve diagnostic accuracy, improve treatment outcomes, decrease costs, and improve patient satisfaction. For the subset of ED patients who would have been inappropriately discharged or unnecessarily admitted, the OU has become a safety net of the ED itself. Like EDs, OUs have progressed from being poorly managed areas of the hospital to the cutting edge of acute health care. The principles developed through past experience and research provide a framework for future developments in emergency medicine.

Emergency Medicine↗
PubMed2001

Cardiac markers protocols in a chest pain observation unit.

The use of cardiac markers to identify high-risk patients in the observation unit is undeniable. As the literature reviewed here reveals, the history and ECG miss a significant portion of patients with acute cardiac ischemia. It appears that acute MI and some high-risk "unstable angina" observation unit patients can be identified within 6 hours of hospital presentation using a combination of cardiac markers. Testing these patients soon after symptom onset or on arrival in the ED for myoglobin, CK-MB subforms, or CK-MB delta appears to provide the best diagnostic usefulness. For testing later in the clinical course, CK-MB troponin I, or troponin T are of clear diagnostic and prognostic value. The markers currently used are unable to identify the significant subset of patients with "non-AMI" coronary syndromes, however. These patients require further testing with appropriate noninvasive or invasive diagnostic studies.

Biomarkers↗
PubMed2001

Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver.

Sinusoidal endothelial cell (SEC) porosities were compared between the periportal (zone 1) and pericentral (zone 3) regions of the rat liver during regeneration following partial hepatectomy (PHx). SEC porosities and fenestration diameters were measured in control livers, as well as at 5 minutes, 24, 48, 72, 96, 120 hours, and 14 days following PHx. Bimodal maximums in both porosity and fenestration diameters were observed in both zones at 5 minutes and 5 days following PHx. SEC porosities increased significantly in both zones 1 and 3 within 5 minutes following PHx, but the increase was maintained only in zone 1 at 24 hours after resection. Following the initial rise, both zones displayed a gradual decrease to less than half their porosity values at 72 hr post-PHx. After 72 hours, porosities increased to over control levels and remained elevated until 14 days after PHx. The decrease in porosity at 72 hr post-PHx is accompanied by ultrastructural changes within the sinusoid at this time. Vascular corrosion casting and transmission electron microscopy (TEM) show sinusoid compression resulting from increased hepatic plate widths due to hepatocyte proliferation in the absence of SEC proliferation. Also at this time, we observed many SEC completely enveloped by stellate cells. The zonal variations observed for porosities throughout regeneration did not correlate with changes in laminin, collagen I and IV, or fibronectin deposition within the space of Disse. Taken together, the data reveal that SEC are dynamic regulators of porosity that respond rapidly and locally to environmental zonal stimuli during liver regeneration.

Animals↗
PubMed2001

Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver.

Regenerating liver was evaluated for the spatiotemporal expression of angiogenic growth factor receptors on endothelial cell (EC) membranes during revascularization resulting from 70% partial hepatectomy (PHx). Fractions enriched in EC membranes were examined by Western blot for angiogenic growth factor receptor expression from 1 to 14 days after PHx. Increases in vascular endothelial growth factor (VEGF) receptors Flt-1 and Flk-1/KDR, angiopoietin receptors Tie-1, Tie-2, and platelet-derived growth factor receptor beta (PDGF-Rbeta), modest increases in epidermal growth factor receptor (EGF-R), and no increase in hepatocyte growth factor receptor (c-Met) or fibroblast growth factor receptors (FGF-R) were observed in isolated membranes during EC proliferation. All receptors were tyrosine phosphorylated, and therefore activated, during peak expression. Immunofluorescence staining of regenerating liver identified populations with increased receptor expression, indicating cells receptive to ligand signaling. EGF-R was upregulated evenly throughout the sinusoidal membrane, whereas c-Met was observed on hepatocyte canaliculae, bile duct epithelium, and large vessel EC. Tie-2 and PDGF-Rbeta were increased on sinusoidal and large vessel EC, whereas Tie-1 was expressed in EC surrounding avascular hepatic islands. Flk-1/KDR was increased on large vessels with slight increases on sinusoidal EC, whereas Flt-1 was increased in arterioles, sinusoidal EC as well as in hepatocytes. Although Flt-1 was phosphorylated on isolated hepatocytes, vascular endothelial growth factor(165) (VEGF(165)) did not induce a proliferative or motogenic response. Proliferation assays on isolated EC indicated responsiveness to VEGF(165), but synergism among several growth factors including PDGF-BB was also observed. The data identify novel autocrine and paracrine interactions and indicate that each growth factor acts on a specific set of EC at specific times during revascularization of regenerating liver.

Animals↗
PubMed2001

Maximizing use of the emergency department observation unit: a novel hybrid design.

STUDY OBJECTIVE: We sought to determine whether sharing an observation unit with scheduled procedure patients would maintain a more consistent unit census and patient/nurse ratio. A secondary objective was to determine the effect of this model on patient length of stay and discharge rates. METHODS: This retrospective, descriptive study was conducted in a high-volume suburban teaching hospital, using a "before-and-after" study design. A "pure" postprocedure unit became a "hybrid" observation postprocedure unit by displacing specific postprocedure patients to inpatient locations. Subsequently, the displaced patients were returned to the unit. On weekends, the unit operated as a pure observation unit. Hourly unit occupancy and census data were prospectively collected, and hourly patient/nurse ratios were calculated. Patient length of stay and discharge data were collected and compared in different settings. RESULTS: The 2 services showed a complementary census pattern that allowed the hybrid unit to maintain an average hourly patient/nurse ratio of 3.7 compared with the ratio of 2.5 for a pure observation unit. There was no difference in observation patient length of stay (14.8 hours versus 14.7 hours) or discharge rate (20.4% versus 18.1%) between weekdays and weekends. However, scheduled procedure patients experienced significantly shorter lengths of stay in the hybrid unit setting (4.3 hours) than in alternative inpatient locations (9.4 hours). CONCLUSION: The hybrid model showed better hourly census and nurse resource use rates, with no adverse effect on observation patients. However, scheduled procedure patient length of stay was shorter in this setting.

Bed Occupancy↗
PubMed2000

Delayed radiation-induced bulbar palsy mimicking ALS.

We describe a patient presenting with progressive bulbar dysfunction and spasticity that clinically mimicked amyotrophic lateral sclerosis (ALS). Electromyography, however, showed no evidence of denervation and revealed a rare combination of peripheral and central myokymia. We feel that this pattern of myokymia represented a marker of neural injury from remote radiation therapy. Nervous system disorders resulting from therapeutic radiation are described, and potential pathophysiologic mechanisms underlying myokymia are discussed.

Bulbar Palsy, Progressive↗
PubMed2000

Association of asthma symptoms and severity with indoor bioaerosols.

BACKGROUND: In this study, repeated measurements were made of levels of mold spores, bacteria, and dust-mite allergens over a 7-month period in the homes of asthmatics, and relationships with measures of asthma severity were evaluated. METHODS: A sample of 57 asthmatic individuals, living in 44 homes in East Moline, Illinois, and nearby communities, participated in a panel study. The homes were visited up to nine times during the study to collect air and dust samples. Asthma severity indicators were derived from questionnaire data and from the daily health records from the panel study. Associations between indoor levels of mold spores, bacteria, and dust-mite allergens were tested with several asthma severity indicators. RESULTS: There was evidence of associations between all asthma severity measures and levels of total and gram-negative bacteria, but mold-spore abundance was associated only with emergency room (ER) visits for asthma. No significant associations were found with house-dust-mite allergen and any of the asthma severity indicators, but the levels of dust-mite allergen were low, with median concentrations of 0.18 microg/g dust Der f 1 and 0.19 microg/g dust Der p 1. CONCLUSIONS: Some evidence was found for associations of increased concentrations of gram-negative bacteria and mold spores with asthma severity, particularly with ER visits. No association was found between house-dust-mite allergen and asthma severity indicators; however, the mite-allergen levels in the study homes were generally well below the proposed threshold level of 2 microg/g dust.

Aerosols↗
PubMed2000

ECG scores for a triage of patients with acute myocardial infarction transported by the emergency medical system.

Prehospital triage of cardiac patients for bypass from community hospitals to cardiac centers may improve survival. This article determines if electrocardiogram (ECG)-based scoring triage methods (Aldrich MI scoring, QRS distortion, and the TIMI classification) and location of infarct (via 12 lead ECG) are associated with mortality before and after adjusting for age, sex, and race. It is a retrospective study of 291 AMI adult patients transported by ambulance to community hospitals or cardiac centers. Patients with an ED chief complaint of chest pain or dyspnea, presence of MI as defined by ECG findings of 0.1 mV of ST segment elevation in two leads or positive CPK-MB were eligible for the study. The primary outcome variable was 2-year mortality as determined with a metropolitan Detroit tri-county death index. Logistic regression was used to calculate the unadjusted and adjusted odds ratios (with 95% CIs) of the predictor variables with mortality. Of the initial population selected for the study (n = 291), 229 patients were eligible for the analysis. The mean age was 66 years (SD of 14.4) with 63.8% being male and 54% being white. The overall mortality point estimate was 21.3% (95% CI of 15.2 to 27.3%). Aldrich scores and QRS distortion (yes/no) were not associated with mortality. Patients classified as a "high risk" for AMI per TIMI status were almost 3 times more likely to die than those at "low risk" and reached borderline statistical significance (P = .06) after adjusting for the covariates. Having an anterior infarct, as opposed to an inferior infarct, was significantly associated with death before and after adjusting for the covariates (Unadjusted OR = 2.6, Adjusted OR = 2.8). Properly training emergency medical system professionals in this area may prove useful for identifying higher risk AMI patients in the prehospital setting.

Aged↗
PubMed2000

A prediction model for prehospital triage of patients with suspected cardiac ischemia.

The American College of Cardiology recommends that patients with high risk acute myocardial infarction (AMI) be triaged to hospitals with percutaneous transluminal coronary angioplasty capability. However, there are no prehospital triage criteria to select candidates for bypassing community hospitals and being taken directly to "cardiac centers." This article assesses which independent variables predict death within 7 days in patients with suspected AMI transported by EMS. This is a retrospective study of 291 AMI patients transported by ambulance to 3 hospitals during 1996-1997. Included were patients who were (n = 244) > or =18 years of age, had a ED chief complaint of chest pain or dyspnea for whom we had mortality data. Mortality at 7 days, our primary outcome measure, was obtained by using a metropolitan Detroit tricounty death index records. Differences between the survivors and nonsurvivors were assessed using the Student's t-test and chi-square tests. Multiple triage criteria were assessed for optimal identification of high risk patients by constructing a logistic multivariate model. Among the study population, 15% died within 7 days (95% confidence interval (CI) 10.3-19.2), and this group represented 63.2% of all deaths over a 2 year surveillance period. Survivors, compared to nonsurvivors, were 14.1 years younger (P < or = .001) and more often men (P < or = 0.001). The dispatch time to ED arrival was less among survivors than nonsurvivors (42.8 vs. 50.6 min, P < or = .01). EMS vital signs differed by survivor status. Among survivors, HR was lower (-11.9 bpm; P < or = 0.01), RR was lower (-6.7 rpm; P < or = .001), SBP was higher (+14.5 mmHg; P < or = 0.05) and DBP was higher (+13.2 mm Hg; P < or = .01). A multivariate model identified the following as independent predictors of early mortality: female gender (OR = 2.3; P < or = .05), age > or =65 (OR = 5.9; P < or = .01), RR > or = 20 (OR = 4.6; P < or = .001), SBP < 120 (OR = 2.4; P < or = .05). The overall model was 86% sensitive and 53% specific with an area under the receiving operating characteristic curve of 0.8 (P < or = .001). A triage rule based on a multivariate model can identify the group at high risk of early cardiac death. This decision rule needs to be prospectively validated.

Aged↗
PubMed2000

Isolated posterior column dysfunction: an unusual presentation of spondylotic myelopathy.

Two patients with previously unreported clinically evident myelopathy caused by herniated intervertebral disks are described. These patients had isolated posterior column dysfunction in the lower extremities without motor deficits, abnormal reflexes, spinothalamic sensory abnormalities, or sphincter changes. The level of cord compression was significantly more cranial than suggested by clinical localization, and the results of initial radiographic studies were unremarkable. Study of posterior column dysfunction using somatosensory evoked potentials was helpful in localizing the lesions and guiding appropriate neuroradiologic studies.

Adult↗
PubMed2000

Analysis of nucleoid morphology during germination and outgrowth of spores of Bacillus species.

After a few minutes of germination, nucleoids in the great majority of spores of Bacillus subtilis and Bacillus megaterium were ring shaped. The major spore DNA binding proteins, the alpha/beta-type small, acid-soluble proteins (SASP), colocalized to these nucleoid rings early in spore germination, as did the B. megaterium homolog of the major B. subtilis chromosomal protein HBsu. The percentage of ring-shaped nucleoids was decreased in germinated spores with lower levels of alpha/beta-type SASP. As spore outgrowth proceeded, the ring-shaped nucleoids disappeared and the nucleoid became more compact. This change took place after degradation of most of the spores' pool of major alpha/beta-type SASP and was delayed when alpha/beta-type SASP degradation was delayed. Later in spore outgrowth, the shape of the nucleoid reverted to the diffuse lobular shape seen in growing cells.

Bacillus megaterium↗
PubMed2000

The Bacillus subtilis HBsu protein modifies the effects of alpha/beta-type, small acid-soluble spore proteins on DNA.

HBsu, the Bacillus subtilis homolog of the Escherichia coli HU proteins and the major chromosomal protein in vegetative cells of B. subtilis, is present at similar levels in vegetative cells and spores ( approximately 5 x 10(4) monomers/genome). The level of HBsu in spores was unaffected by the presence or absence of the alpha/beta-type, small acid-soluble proteins (SASP), which are the major chromosomal proteins in spores. In developing forespores, HBsu colocalized with alpha/beta-type SASP on the nucleoid, suggesting that HBsu could modulate alpha/beta-type SASP-mediated properties of spore DNA. Indeed, in vitro studies showed that HBsu altered alpha/beta-type SASP protection of pUC19 from DNase digestion, induced negative DNA supercoiling opposing alpha/beta-type SASP-mediated positive supercoiling, and greatly ameliorated the alpha/beta-type SASP-mediated increase in DNA persistence length. However, HBsu did not significantly interfere with the alpha/beta-type SASP-mediated changes in the UV photochemistry of DNA that explain the heightened resistance of spores to UV radiation. These data strongly support a role for HBsu in modulating the effects of alpha/beta-type SASP on the properties of DNA in the developing and dormant spore.

Bacillus subtilis↗
PubMed1999

Multisystem neuronal involvement and sicca complex: broadening the spectrum of complications.

We report two patients with multisystem neuronal involvement associated with sicca complex. One had a lower motor neuron syndrome combined with a flaccid bladder and rectum. The second patient had unilateral hearing loss, sensory neuronopathy, Adie's pupils, upper motor neuron signs, and autopsy-proven anterior horn cell degeneration. Our cases lead us to propose that the spectrum of neuronal involvement occurring with sicca syndrome may be wider than is currently appreciated.

Adie Syndrome↗
PubMed1999

Cationic colloidal silica membrane perturbation as a means of examining changes at the sinusoidal surface during liver regeneration.

By employing the cationic colloidal silica membrane density perturbation technique, we examined growth factor receptor and extracellular matrix (ECM) changes at the sinusoidal surface during rat liver regeneration 72 hours after 70% partial hepatectomy (PHx). At this time after PHx, hepatocyte division has mostly subsided, while sinusoidal endothelial cell (SEC) proliferation is initiating, resulting in avascular hepatocyte islands. Because of the discontinuous nature of the surface of liver SEC, ECM proteins underlying the SEC, as well as SEC luminal membrane proteins, are available to absorption to the charged silica beads when the liver is perfused with the colloid. Subsequent liver homogenization and density centrifugation yield two separate fractions, enriched in SECs as well as hepatocyte basolateral membrane-specific proteins up to 50-fold over whole liver lysates. This technique facilitates examination of changes in protein composition that influence or occur as a result of SEC mitogenesis and migration during regeneration of the liver. When ECM and receptor proteins from SEC-enriched fractions were examined by Western immunoblotting, urokinase plasminogen activator receptor, fibronectin, and plasmin increased at the SEC surface 72 hours after PHx. Epidermal growth factor receptor, plasminogen, SPARC (secreted protein, acidic and rich in cysteine, also called osteonectin or BM40), and collagen IV decreased, and fibrinogen subunits and c-Met expression remained constant 72 hours after PHx when compared to control liver. These results display the usefulness of the cationic colloidal silica membrane isolation protocol. They also show considerable modulation of surface components that may regulate angiogenic processes at the end stage of liver regeneration during the reformation of sinusoids.

Animals↗