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Biomedical subjects

J Ross

Publications and source records attributed to J Ross.

At least 19 recordsLinked to original sources

Low-dose (7.5 mg) oral methotrexate for chronic progressive multiple sclerosis. Design of a randomized, placebo-controlled trial with sample size benefits from a composite outcome variable including preliminary data on toxicity.

OBJECTIVE: To present a detailed description of (1) the study design of this ongoing trial, (2) advantages of using a composite outcome variable instead of multiple individual outcome measures, (3) treatment group characteristics at baseline, and (4) observed short-term methotrexate (MTX) toxicity. DESIGN: Randomized, double-masked, placebo-controlled intervention study. SETTING: Referral-based outpatient multidisciplinary multiple sclerosis (MS) clinic. PATIENTS: Participation offered to all clinically definite chronic progressive multiple sclerosis (CPMS) patients attending clinic ages 21 to 60, disease duration > 1 year, Expanded Disability Status Scale (EDSS) score 3.0 to 6.5 (ambulatory with moderate disability). Patients first stratified by EDSS 3.0 to 5.5 and 6.0 to 6.5, then randomized to MTX or placebo treatment. INTERVENTION: Weekly oral low-dose (7.5 mg) MTX or identical-appearing placebo for 2 years followed by a 1-year observation period. MAIN OUTCOME MEASURES: Sample size calculations undertaken prior to enrolling patients based upon a composite outcome variable consisting of designated change in any of the following functional measures: (1) EDSS, (2) Ambulation Index (AI), (3) Box and Block Test (BBT), and (4) 9-Hole Peg Test (9HPT). RESULTS: (1) Treatment group characteristics were comparable at baseline, (2) no patient has been withdrawn for adverse effects or lost to follow-up, (3) no significant short-term MTX toxicity has been observed. CONCLUSIONS: (1) The use of a composite outcome measure in the design of MS clinical trials is a promising alternative to multiple individual outcome measures that are relatively insensitive to detecting clinical change, (2) low-dose oral weekly MTX does not appear to be associated with significant short-term toxicity in CPMS. Conclusions regarding therapeutic efficacy of MTX in MS must await completion of this clinical trial.

Adult

Improved processes for the production and isolation of dynemicin A and large-scale fermentation in a 10,000-liter fermentor.

Supplementing the culture of Micromonospora chersina sp. nov. No. M956-1 with NaI (0.5 mg/l) enhanced the production of dynemicin A by 35-fold in shake flask culture. Homogeneous dynemicin A was obtained from the whole broth extract by Dicalite chromatography, Sephadex LH-20 chromatography and vacuum liquid chromatography. Gram quantities of dynemicin A were obtained from the fermentation of M. chersina sp. nov. No. M956-1 in a 10,000-liter fermentor.

Anthraquinones

Enhancement of the force-frequency effect on myocardial contractility by adrenergic stimulation in conscious dogs.

BACKGROUND: The influence of changes in heart rate on myocardial contractility (the force-frequency effect) differs under various experimental conditions, including the anesthetized versus the conscious state. METHODS AND RESULTS: To assess the influence of beta-adrenergic stimulation on force-frequency effects on myocardial contraction and relaxation, seven instrumented conscious dogs were studied in which heart rate could be controlled by atrial pacing after the intrinsic rate was slowed with a bradycardiac agent (UL-FS 49 0.5-0.75 mg/kg). Left ventricular (LV) pressure was measured with a micromanometer under resting conditions and during dobutamine infusion at low, intermediate, and high doses (2.7, 5.4, and 10.7 micrograms/kg/min). At each dose, heart rate was progressively increased from 100 to 210 beats per minute. In the absence of dobutamine (control), no significant positive force-frequency effect was detected on LV dP/dtmax; this was probably due to the known effect of the observed decrease in preload to reduce LV dP/dtmax, thereby offsetting an effect of the force-frequency response to increased dP/dt. However, during dobutamine infusions, the force-frequency effect was observed to increase significantly in a dose-dependent manner with increases in heart rate. An increase in heart rate from 100 to 210 beats per minute increased LV dP/dtmax by 12.4 +/- 12.5% with low-dose, 22.7 +/- 13.1% with intermediate-dose, and 27.5 +/- 8.9% with high-dose dobutamine. Changes in preload and aortic pressure were within the same ranges under control conditions and at each of the three dobutamine doses. The time constant of LV pressure fall (tau) was significantly shorter with increases in heart rate during control, but only the highest dobutamine dose caused further significant shortening in tau with increased heart rate. CONCLUSIONS: These data indicate that there is a pronounced dose-dependent action of beta-adrenergic stimulation to enhance force-frequency-induced contractile responses in normal conscious dogs.

Adrenergic beta-Agonists

Myxomatosis: population dynamics of rabbits (Oryctolagus cuniculus Linnaeus, 1758) and ecological effects in the United Kingdom.

In 1953-1955, myxomatosis spread among rabbits (Oryctolagus cuniculus) in the United Kingdom, causing 99% mortality. Subsequently, there was a gradual increase in rabbit numbers. By 1955, the Ministry of Agriculture, Fisheries and Food (MAFF) had already found attenuated strains of myxoma virus. By 1970, genetic resistance had appeared. In the 1970s, mortality declined to 47-69% with only approximately 25% of rabbits infected, giving a field mortality of 12-19%. However, myxomatosis is persistent, generally showing a major prevalence peak in autumn and often a minor peak in spring. An eight-year MAFF experiment in which prevalence of the disease was artificially reduced indicates that myxomatosis remains a significant factor in population regulation. After rabbit numbers fell in the 1950s, important ecological changes took place: vegetation altered due to reduced grazing pressure, predators were affected by the reduction of a major prey species and these changes also affected many other animals. Currently, rabbit numbers have returned to approximately one-third of pre-myxomatosis levels and this is causing damage to farm and conservation habitats.

Animals

Disappearance of Q waves following thrombolysis for acute myocardial infarction.

The development of Q waves on the surface electrocardiogram generally is considered indicative of myocardial infarction. Such Q waves are usually permanent, though may regress and disappear over months to years. Transient Q waves have been described during myocardial ischemia without evidence of infarction. More recently, Q waves have been noted to develop transiently during the acute phases of infarction, possibly representing stunned myocardium. In this case report, a patient with an evolving anterior myocardial infarction and new septal Q waves was treated with intravenous thrombolytic therapy. Three hours following treatment the patient was clinically improved, and the septal Q waves had been replaced by small but obvious R waves. Despite a large area of myocardium at risk of infarction on the initial electrocardiogram, the resultant infarction was enzymatically and echocardiographically small. Early Q waves in acutely evolving myocardial infarction may represent severely ischemic, rather than irreversibly damaged, myocardium which may still be salvaged with thrombolytic therapy.

Adult