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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 RESULTS: (1) Treatment group characteristics were comparable at baseline, (2) no patient has been withdrawn for adverse effects or lost to follow-up, (3) no significant short-term MTX toxicity has been observed.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

Chemical implementation and thermodynamics of collective neural networks.

The chemical implementation of a neuron and connections among neurons described in prior work is used to construct collective neural networks. With stated approximations, these chemical networks are reduced to networks of the Hopfield type. Chemical networks approaching a stationary or equilibrium state provide a Liapunov function with the same extremal properties as Hopfield's energy function. Numerical comparisons of chemical and Hopfield networks with small numbers (2-16) of neurons show agreement on the results of given computations.

Catalysis

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

Spatial frequency tuning of facilitation by masks.

The spatial frequency tuning of facilitation by masks is derived for a 2 c/deg test grating, counterphased at 8.8 Hz, from the contrasts at which masks of different spatial frequencies facilitate maximally. This tuning function has a bandwidth at half height of roughly 1.5 octaves, much broader than has been estimated previously from tuning functions determined at a constant contrast for each mask. We show also that best facilitation more than doubles sensitivity for tests of 4 c/deg and below, and that the magnitude of the facilitation effect declines at higher spatial frequencies.

Contrast Sensitivity

Dysphagia as a major symptom of tetanus.

Dysphagia is a common symptom presenting to ENT departments. Two cases of tetanus with dysphagia as a major symptom are discussed, together with a review of previously reported cases. Although tetanus is a rare disease in the United Kingdom, the possibility of this diagnosis should be borne in mind in patients presenting with progressive dysphagia, especially if there are other head and neck symptoms present.

Barium Sulfate

The role of value orientations in curricular decision making: a rationale for teachers' goals and expectations.

This research examined the role of value orientations in curricular decision making from the perspective of high school physical education teachers and students. Educational value orientations served as the theoretical base for the research. Teachers who exhibited one of two paired orientations, disciplinary mastery/learning process (DM/LP) or ecological integration/social reconstruction (EI/SR), were interviewed to examine the extent to which their value orientations influenced their stated (a) goals for student learning, and (b) expectations for academic performance and behavior. Students were also interviewed to investigate the extent to which they acknowledged these goals and expectations. Data were analyzed using constant comparison. Results suggested that goals and expectations of DM/LP and EI/SR teachers were distinctly different and that comments from students in the EI/SR teachers' classes did not reflect their teachers' goals and expectations. Dynamical system theory was used to conceptualize value orientations as attractors within the educational ecosystem. Teachers working from weak EI/SR value attractors may be limited by learner, instructional, and contextual constraints.

Curriculum

The effect of postural drainage positioning on ventilation homogeneity in healthy subjects.

Body position is known to have significant effects on oxygen transport. These effects, however, are seldom considered during postural drainage (PD). The purpose of this study was to examine the effect of modified PD positions on ventilation homogeneity (the evenness of the distribution of ventilation), which is a key component of oxygen transport. The single-breath nitrogen washout test was used to obtain an index of ventilation homogeneity (slope of phase 3 [SBN2/L%]). Seventeen healthy individuals, ranging from 22 to 40 years of age ( mean = 28.4, SD = 5.6), performed the single-breath nitrogen test while sitting, lying supine with the bed tipped head down, right side lying, and right side lying with the bed tipped head down. Within-subject one-way analyses of variance and Tukey's post hoc analyses were used to compare differences in SBN2/L% across the four positions. The distribution of ventilation was significantly less homogeneous in the side-lying positions compared with the supine and sitting positions. Although these results reflect a position-induced change in pleural pressure gradient, they also reflect the effect of gravity-independent, intraregional changes on ventilation distribution. Thus, modified PD positioning has a significant effect on ventilation homogeneity, which may predispose a patient to arterial desaturation. Given the complexity of the factors involved, patients considered for PD positioning should be monitored for arterial saturation.

Adult

Control of c-myc mRNA half-life in vitro by a protein capable of binding to a coding region stability determinant.

Polysome-associated c-myc mRNA is degraded relatively rapidly in cells and in an in vitro mRNA decay system containing extracts from cultured mammalian cells. Using this system, a competition/screening assay was devised to search for factors that bind to specific regions of polysome-associated c-myc mRNA and thereby alter its half-life. mRNA stability was first assayed in reactions containing exogenous competitor RNAs corresponding to portions of c-myc mRNA itself. The addition of a 182-nucleotide sense strand fragment from the carboxy-terminal portion of the c-myc-coding region destabilized c-myc mRNA by at least eightfold. This RNA fragment had no effect on the stability of other mRNAs tested. Moreover, c-myc mRNA was not destabilized in reactions containing unrelated competitor RNAs or sense strand RNA from the c-myc 5' region. Polysome-associated globin mRNA containing the c-myc-coding region segment in-frame was also destabilized in vitro by the 182-nucleotide RNA. As determined by UV-cross-linking experiments, the 182-nucleotide RNA fragment was recognized by and bound to an approximately 75-kD polysome-associated protein. On the basis of these data plus Northern blotting analyses of c-myc mRNA decay products, we suggest that the approximately 75-kD protein is normally bound to a c-myc-coding region determinant and protects that region of the mRNA from endonuclease attack. Possible links between the protective protein, translation, ribosome pausing, and c-myc mRNA turnover are discussed.

Base Sequence

Cutaneous malignant melanoma and human immunodeficiency virus (HIV) infection: a report of three cases.

Cutaneous malignant melanoma was diagnosed in three patients suffering from human immunodeficiency virus (HIV) infection. Staging at presentation inversely correlated with absolute CD4 count. In addition, a notably sparse lymphocytic inflammatory response to the melanoma was observed in two cases. Established data on melanoma in non-HIV immunosuppressed patients suggests a poor prognosis for melanoma in HIV disease.

Adult

Formant frequencies in Estonian folk singing.

Formant frequencies in an old Estonian folk song performed by two female voices were estimated for two back vowels /a/ and /u/, and for two front vowels /e/ and /i/. Comparison of these estimates with formant frequencies in spoken Estonian vowels indicates a trend of the vowels to be clustered into two sets of front and back ones in the F1/F2 plane. Similar clustering has previously been shown to occur in opera and choir singing, especially with increasing fundamental frequency. The clustering in the present song, however, may also be due to a tendency for a mid vowel to be realized as a higher-beginning diphthong, which is characteristic of the North-Estonian coastal dialect area where the singers come from. No evidence of a "singer's formant" was found.

Estonia

A serovar analysis of heterosexual gonorrhoea in Edinburgh 1986-90.

OBJECTIVE: To analyse the frequency of different gonococcal serovars within Edinburgh, Scotland and to describe changes that occurred in the frequency of such serovars over time. METHODS: All heterosexual patients with a diagnosis of gonorrhoea confirmed on culture between January 1986 and December 1990 had their gonococcal strain serotyped. Temporal changes in the prevalence of gonorrhoea and the serovar of the isolates were analysed. RESULTS: Isolates of Neisseria gonorrhoeae from 1356 episodes of gonorrhoea were serotyped. Three serovars, Bajk (IB-3/IB-6), Bacejk (IB-1/IB-2) and Aedgkih (IA-1/IA-2), dominated, occurring in two-thirds of all infections. Over the study period Bajk (IB-3/IB-6) and Aedgkih (IA-1/IA-2) isolates declined in frequency in parallel with an overall fall in the prevalence of gonorrhoea but Bacejk (IB-1/IB-2) persisted at a lower but fairly constant level. Despite a fall in the number of gonococcal infections the variety of new serovars being isolated fluctuated. CONCLUSIONS: The ability of some serovars to persist while others decline in incidence may be partially related to antibiotic sensitivities but other factors such as an ability to evade the immune response and transfer of serovars from one population group to another may also be important.

Antigens, Bacterial

Influence of the force-frequency relation on left ventricular function during exercise in conscious dogs.

BACKGROUND: The magnitude of the force-frequency effect on myocardial contractility in the conscious animal has been studied at rest, but it has not been assessed during exercise. METHODS AND RESULTS: The influence of heart rate (HR) changes were evaluated during treadmill exercise in eight preinstrumented, conscious dogs in which high-fidelity left ventricular (LV) pressure, LV volume (by sonomicrometry), and aortic pressure were measured. Under resting conditions, end-systolic pressure-volume relations were obtained using inferior vena caval occlusion. Dogs were run on a treadmill, and the intrinsic exercise HR was reduced by infusion of a specific bradycardic drug (UL-FS 49 0.5 mg/kg) during continuing exercise while HR was maintained at 240 beats per minute by atrial pacing. At 6 minutes of running at a fixed, paced HR when a stable drug effect had been achieved, no effects of UL-FS 49 on measures of LV contractility were detected compared with exercise before drug administration. HR was then reduced stepwise from 240 to 210, 180, or 150 beats per minute in a random manner, returning to 240 beats per minute between steps. Progressive reductions in measures of myocardial contractility occurred as the HR was slowed, and reduction of rate from 240 to 150 beats per minute reduced the LV maximum positive dP/dt by 31% and (dP/dt)DP40 by 21% despite increases in LV end-diastolic pressure. The entire end-systolic pressure-volume could not be determined during exercise, but beat-averaged end-systolic pressure-volume points during exercise were progressively shifted to the right and downward by slowing the exercise HR. Thus, a pronounced negative inotropic influence of slowing the heart was observed during exercise, and the rate of ventricular relaxation (tau) was also significantly prolonged. CONCLUSIONS: These findings indicate that force-frequency effects on the inotropic state of the intact LV are markedly enhanced by exercise.

Animals

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

Myocardial function and transmural blood flow during coronary venous retroperfusion in pigs.

BACKGROUND: The degree of recovery of regional myocardial contraction during coronary venous retroperfusion has not been well established, particularly in the absence of coronary collateral channels. Therefore, the maximal functional benefit attainable with coronary venous retroperfusion was assessed in pigs by means of using selective pump retroperfusion of the left anterior descending vein, with venting of the left anterior descending artery to zero pressure. METHODS AND RESULTS: In eight anesthetized open-chest pigs during selective left anterior descending venous retroperfusion over a range of retroperfusion flows, regional myocardial function (percent systolic wall thickening by sonomicrometry) increased progressively to an average of 62% of control values at a retroperfusion flow rate 200% of control arterial flow. Progressive thickening of the end-diastolic dimension of the anterior wall was observed with increasing retroperfusion flow (from 8.7 +/- 0.9 to 10.7 +/- 2.3 mm, p less than 0.001). Perfusion pressures within the left anterior descending vein increased linearly with increased retroperfusion flow rates (up to 132 +/- 57 mm Hg with retroperfusion flow 200% of control). A gradual increase of retrograde left anterior descending arterial outflow was observed with increasing retroperfusion flows; however, the absolute amount (maximum, 8.3 +/- 4.1 ml/min) was much too low to explain the extent of functional recovery. Transmural myocardial capillary blood flows in the anterior wall with retroperfusion flows of 100% and 200% of control arterial flow were 0.22 and 0.42 ml/min/g with corresponding subendocardial blood flows of 0.14 and 0.29 ml/min/g; ratios of endocardium to epicardium were 0.51 and 0.61, respectively. Thus, capillary blood flows during selective retroperfusion were relatively low despite considerable restoration of regional systolic wall thickening, and a significant difference was noted in the slopes of the relations between regional systolic wall thickening and myocardial blood flow during retroperfusion and anterograde arterial perfusion (p less than 0.05). With retrograde injection of silicone elastomer at different retroperfusion pressures (50, 75, and 100 mm Hg) in three pigs, capillaries were well visualized, and profuse intramyocardial venous anastomotic connections were seen at the highest retroperfusion pressure (100 mm Hg), whereas there was filling of small venules but little capillary filling at the lowest retroperfusion pressure (50 mm Hg). CONCLUSIONS: Considerable recovery of regional myocardial function with low regional capillary blood flows were observed during acute venous retroperfusion with high retroperfusion flows with arterial blood. These findings together with low levels of retrograde arterial outflow and visualization of retrograde capillary filling with a rich venous network provide evidence for possible oxygen delivery via the intramyocardial venous plexus.

Animals