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Biomedical subjects

M Scott

Publications and source records attributed to M Scott.

At least 397 records · Page 22Linked to original sources
PubMedDate not supplied

Assessment of the value of therapeutic monitoring of tacrine in Alzheimer's disease.

OBJECTIVES: The purpose of this study was to validate the lower end of the putative therapeutic range of serum tacrine concentrations of 7-20 ng ml(-1) in the treatment of Alzheimer's disease. METHODS: The relationship between dose, steady-state serum tacrine concentrations and change in MMSE score (a measure of cognitive function) was examined in 106 Alzheimer's disease patients who had been treated with the drug for 12 weeks. RESULTS: In all, 72% of patients showed some response, but there was no relationship between dose and the chance of a favourable outcome. The proportion of patients with serum concentrations above 7 ng x ml(-1) who improved (79%) was significantly greater than that of those with serum concentrations below this level (47%) (P < 0.02). Also, a significantly greater proportion of patients with serum concentrations above both 5 ng x ml(-1) and 9 ng x ml(-1) showed improvement in comparison to those with concentrations below these levels. CONCLUSIONS: This study indicates that therapeutic monitoring of serum tacrine concentrations might increase the possibility of responding to tacrine by some 68%. This represents an important contribution to the management of Alzheimer's disease patients with this drug, and may also be relevant to the use of the newer generation of cholinesterase inhibitors.

Aged↗
PubMedDate not supplied

Delayed and occult splenic rupture.

Four patients with delayed splenic rupture were evaluated by CT or US and liver-spleen scan. The cases and radiographic findings and their significance are presented. The importance of this entity, in light of recent surgical trends, is discussed.

Adult↗
PubMedDate not supplied

Comparison of colour Doppler imaging of orbital vessels in elderly compared with young adult patients.

PURPOSE: Colour Doppler imaging provides an estimate of the velocity of blood flow in vessels supplying the eye. METHODS: To assess changes in orbital blood flow with age, we used a method to study peak systolic velocity in 20 young normal patients, mean age 25.2+/-2.4 years and 30 elderly normal patients, mean age 69.5+/-7.9 years. RESULTS: Peak systolic velocity was significantly higher in the central retinal artery and the temporal division of the posterior ciliary artery in elderly patients. There was greater variation in the peak systolic velocity readings in the distal part of the ophthalmic artery in the elderly than in the younger group. There was greater variation in the pulsatility index in the central retinal artery in young subjects. CONCLUSIONS: Though not large, these differences suggest changes in the orbital blood vessels with age which could affect the development of disease processes in elderly patients. These changes should be taken into account when assessing blood flow in elderly patients.

Adult↗
PubMedDate not supplied

Kinetics and specificity at the clonal level of the cytotoxic T lymphocyte response to influenza pneumonia.

We have studied the kinetics and specificity of the cytotoxic T lymphocyte (CTL) response to influenza A/PR/8 (H1N1) virus pulmonary infection in the mouse detected using spleen cells from infected mice which were stimulated in bulk and limiting dilution cultures. A hybrid protein designated D-peptide, which contains the terminal 157 amino acids of the HA2 subunit of A/PR/8 virus, was used to stimulate influenza virus subtype-specific secondary CTL in vitro. Infection induced two specificities of precursor CTL, cross-reactive and subtype-specific. The kinetics of the subtype-specific CTL response detected by the D-peptide were similar to the cross-reactive CTL response detected by stimulation with live virus. The majority of the precursor CTL (CTL-p) are able to lyse virus-infected target cells in a cross-reactive fashion. The number of memory subtype-specific and cross-reactive CTL increased by approximately 2.5 logs10 during the first 3 weeks after infection.

Administration, Intranasal↗
PubMedDate not supplied

A study of the interaction between dirithromycin and astemizole in healthy adults.

The effect of a standard regimen of dirithromycin, a macrolide antibiotic, on the single-dose pharmacokinetics of the H (1) receptor blocker astemizole was evaluated in a sample of 18 healthy young adults (nine males and nine females). The study was conducted in a two-way cross-over fashion after the subjects had been randomly given either dirithromycin (two 250 mg tablets) or placebo (two tablets) every morning for 10 days. On the morning of the fourth dose of either dirithromycin or placebo each subject ingested a single 30-mg oral dose (three 10-mg tablets) of astemizole. The disposition kinetics of both astemizole and its major metabolite, N-desmethylastemizole, were characterized after measuring the concentrations of both analytes in the serum fraction of serial blood samples collected for 14 days after the astemizole dose. In addition, corrected QT (QT(c) ) intervals were estimated from electrocardiogram rhythm strips that were run 24 hours prior to the astemizole dose, 12 hours after the astemizole dose, and after the last treatment (dirithromycin or placebo) dose in both study periods. Pharmacokinetic parameters that were measured for both astemizole and N-desmethylastemizole during each treatment were: C(max), t(max), AUC (0-infinity), CL(oral), half-life, and volume of distribution (V). None of the parameters for N-desmethylastemizole was different when comparing data by ANOVA from the dirithromycin treatment period with that of the placebo treatment period. On the other hand, during dirithromycin treatment astemizole CL(oral) was 34% slower, volume of distribution was 24% larger, and half-life was 84% longer. Generally, all QT ( c ) intervals did not appear to be affected by dirithromycin treatment. The changes in astemizole kinetics could not be attributed to its N-demethylation since the dispositional kinetics of N-desmethylastemizole were unaffected by dirithromycin. Therefore, it is difficult to ascertain the clinical significance of the changes in astemizole kinetics. Since there were no significant differences for mean QT(c) intervals and no effect of dirithromycin treatment on N-desmethylastemizole kinetics, it is unlikely that a standard regimen of dirithromycin would place a patient taking astemizole at an increased risk of torsade de pointes or related ventricular arrhythmias.

Adolescent↗
PubMedDate not supplied

The evolution of walking-related outcomes over the first 12 weeks of rehabilitation for incomplete traumatic spinal cord injury: the multicenter randomized Spinal Cord Injury Locomotor Trial.

BACKGROUND: The Spinal Cord Injury Locomotor Trial (SCILT) compared 12 weeks of step training with body weight support on a treadmill (BWSTT) that included overground practice to a defined but more conventional overground mobility intervention (CONT) in patients with incomplete traumatic SCI within 8 weeks of onset. No previous studies have reported walking-related outcomes during rehabilitation. METHODS: This single-blinded, randomized trial entered 107 American Spinal Injury Association (ASIA) C and D patients and 38 ASIA B patients with lesions between C5 and L3 who were unable to walk on admission for rehabilitation. The Functional Independence Measure (FIM-L) for walking, 15-m walking speed, and lower extremity motor score (LEMS) were collected every 2 weeks. RESULTS: No significant differences were found at entry and during the treatment phase (12-week mean FIM-L = 5, velocity = 0.8 m/s, LEMS = 35, distance walked in 6 min = 250 m). Combining the 2 arms, a FIM-L >or= 4 was achieved in < 10% of ASIA B patients, 92% of ASIA C patients, and all of ASIA D patients. Walking speed of >or= 0.6 m/s correlated with a LEMS near 40 or higher. CONCLUSIONS: Few ASIA B and most ASIA C and D patients achieved functional walking ability by the end of 12 weeks of BWSTT and CONT, consistent with the primary outcome data at 6 months. Walking-related measures assessed at 2-week intervals reveal that time after SCI is an important variable for entering patients into a trial with mobility outcomes. By about 6 weeks after entry, most patients who will recover have improved their FIM-L to >3 and are improving in walking speed. Future trials may reduce the number needed to treat by entering patients with FIM-L < 4 at > 8 weeks after onset if still graded ASIA B and at > 12 weeks if still ASIA C.

Adult↗
PubMedDate not supplied

Noninvasive measurement of regional lung water distribution in healthy man and in pulmonary oedema.

A quasi steady-state noninvasive, radioisotopic technique for measuring regional lung water distribution in man is described. The method depends upon the dilution principle. 123I labelled human serum albumin (HSA) and sodium iodide (NaI) were injected intravenously, allowed to mix completely within the body fluids and then counted externally over the chest. The size of each compartment to which the markers are confined was calculated from the external count rate and the isotopic concentration of the marker in plasma. 123I-HSA was used to estimate intravascular water and 123I-NaI extracellular water. Ratio analysis of the differential attenuation of the two photoenergies of 123Iodine (29 keV, 159 keV) by the lung and chest wall was used to estimate the absolute amount of isotope in the lung, independent of chest wall contribution, after validation by phantom studies. Regional pulmonary plasma (PPVr) and interstitial (PIVr) fluid volumes in normal subjects were 7.1 +/- 1.4 and 7.6 +/- 1.3 ml.100 cm-3 lung (mean +/- SD; n = 13) at mid-tidal volume, respectively. In patients with the adult respiratory distress syndrome, PPVr and PIVr were 7.0 +/- 2.9 and 15.9 +/- 4.6 ml.100 cm-3 lung (n = 18), respectively. The pulmonary artery wedge (Paw) pressure was normal (12.5 +/- 2.5 mmHg; n = 5). In patients with pulmonary oedema due to left heart disease, PPVr and PIVr were 7.2 +/- 2.7 and 12.1 +/- 3.7 ml.100 cm-3 lung (n = 8), respectively. The mean Paw pressure in this group was high (28.5 +/- 3.9 mmHg).

Adult↗