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Biomedical subjects

P Stone

Publications and source records attributed to P Stone.

At least 73 records · Page 4Linked to original sources

Bronchodilator reversibility, exercise performance and breathlessness in stable chronic obstructive pulmonary disease.

Partial bronchodilator reversibility can be demonstrated in many patients with stable chronic obstructive pulmonary disease (COPD), but its relevance to exercise capacity and symptoms is uncertain. Previous data suggest that anticholinergic bronchodilators do not improve exercise tolerance in such patients. We studied 32 patients with stable COPD, mean age 65 yrs, in a double-blind, placebo-controlled, cross-over trial of the inhaled anticholinergic drug, oxitropium bromide. From the within and between day placebo spirometry, we derived the spontaneous variation in forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) of this population (FEV1 140 ml; FVC 390 ml) and considered responses beyond this to be significant. Oxitropium bromide increased baseline FEV1 from 0.70 (0.28) l (mean (SD)) to 0.88 (0.36) l. The 6 min walking distance increased by 7% compared with placebo, whilst resting breathlessness scores fell from 2.0 to 1.23 at rest and 4.09 to 3.28 at the end of exercise after the active drug. Improvements in walking distances and symptoms were unrelated to changes in either FEV1 or FVC, indicating that routine reversibility testing is not a good predictor of symptomatic benefit in these patients.

Aged↗

Cost of intensive therapy. A description of methodology and initial results.

A preliminary study was performed to calculate the cost of intensive therapy on an individual patient basis. The fixed (equipment, supporting services and land opportunity), semi-fixed (staff) and marginal (treatment) costs of 20 critically ill patients were calculated individually. The results show that there is wide variation in intensive therapy costs. The average daily cost for a spontaneously breathing patient was 399 pounds (95% confidence intervals 388 pounds-460 pounds) while that for a ventilated patient was 726 pounds (656 pounds-795 pounds). The mean total cost per patient was 1980 pounds, but the cost per survivor increased by 16% (347 pounds) because of four deaths on the intensive care unit. High total costs are associated with increased severity of illness and higher marginal (treatment) costs are associated with increased semi-fixed (staff) costs. The cost of intensive therapy was three to five times that for general ward care.

Adult↗

Attenuation of nocturnal asthma by cromakalim.

In a randomised, double-blind, crossover study, single oral doses of cromakalim, a potassium-channel activator, or placebo were given to 23 patients with nocturnal asthma. There was a significant reduction (p less than 0.005) in the early morning fall in forced expiratory volume in 1 s (FEV1) after 0.5 mg cromakalim (fall 9.8% [SEM 3.2%]) compared with placebo (18.5 [2.8]%). In a repeat dosing study, administration of 0.25 mg and 0.5 mg cromakalim on 5 consecutive nights to a further group of 8 asthmatic subjects significantly reduced the early morning fall in FEV1 from 28.7 (6.5)% after placebo to 19 (4.2)% after 0.25 mg and 14.9 (6.5)% after 0.5 mg. Potassium-channel activators may be useful in the treatment of asthma, especially for nocturnal symptoms.

Adult↗

Ultradian rhythms in responsiveness to stimuli presented during sleep.

The present study examined rhythmicity in responding to stimuli presented during sleep. Subjects were trained while awake to respond (by taking a deep breath) to an auditory stimulus that was subsequently presented after every 4 min (8 subjects) or after every 1 min (8 subjects) of continuous sleep. Visual inspection of the response data revealed, for most subjects, a tendency for response latencies to vary rhythmically with 3-5 response cycles per night. Relatively slow, "time-of-night", changes in responsiveness were also seen. Spectral analysis supported the observation of response rhythmicity. Frequency bands with centers corresponding to periods of 133, 100, and 80 min accounted for a significant proportion of the spectral variance for both the 4-min and 1-min group. Sleep was severely disrupted under the 1-min condition, but response rhythmicity was as evident as under the 4-min condition. For subjects having nearly normal sleep structure, the longer latencies in the response cycles tended to occur during nonrapid eye movement periods, while the shorter latencies tended to occur near REM. Response variability during REM often obscured cyclic tendencies. The data suggest that responsiveness during sleep

Acoustic Stimulation↗

Congenital tracheal stenosis in Pfeiffer syndrome.

We report an infant with Pfeiffer syndrome (acrocephalosyndactyly type V) and a solid cartilaginous trachea lacking rings. This airway abnormality has been reported in a child with Crouzon syndrome but has not been described in Pfeiffer syndrome.

Acrocephalosyndactylia↗

Measurement of anterior-posterior displacement of the knee. A comparison of the results with instrumented devices and with clinical examination.

Thirteen subjects who had normal knees and fifteen patients who had a chronic rupture of the anterior cruciate ligament were tested in order to compare the measurements of tibiofemoral displacement as recorded by four commercial devices: the Acufex knee-signature system, the Genucom knee-analysis system, the Medmetric KT-1000 arthrometer, and the Stryker knee-laxity tester. Anterior and posterior displacement were measured at forces of eighty-nine newtons (twenty pounds) and 133 newtons (thirty pounds). We found significant differences in reproducibility of measurement among the devices. The Acufex, Medmetric, and Stryker devices had more reproducible measurements, and they could be used to identify 80 to 90 per cent of the normal subjects and anterior cruciate-deficient patients. The Genucom device had poorer reproducibility of measurement, and it tended to register greater differences in displacement between the right and left knees of normal subjects.

Adult↗

Attention deficit disorder with and without hyperactivity: reaction time and speed of cognitive processing.

This study addressed the issue as to whether children reliably diagnosed as attention deficit disordered with hyperactivity (ADD/H) and without hyperactivity (ADD/WO) differed significantly from each other and a clinic control (CC) population on speed and efficiency of cognitive processing. From an outpatient clinic population, 43 ADD/H and 22 ADD/WO children were examined. An analysis of mean reaction time and speeded classification task performance revealed significant group effects on both mean reaction time and on a measure of within-subject variability. ADD/H children performed significantly more slowly and variably than the CC children on several of the speeded classification tasks. However, the ADD/WO group was not distinguished on any measure. Thus, while children may be reliably diagnosed as ADD/H or ADD/WO using behavioral measures, it would appear that they cannot be distinguished on these neurocognitive tasks. Issues related to childhood psychopathology and the neuropsychological basis of ADD/H are discussed.

Age Factors↗

A controlled trial of an oral bronchodilator preparation ('Franol') in asthma.

In view of the lack of published data on the oral bronchodilator preparation 'Franol' (120 mg theophylline, 11 mg ephedrine hydrochloride and 8 mg phenobarbitone per tablet) a double-blind study was carried out to compare the effects on lung function of a single dose of 2 'Franol' tablets, 1 'Franol' plus 1 placebo tablet, or 2 placebo tablets over a period of 8 hours in 30 asthmatic patients with reversible airways resistance (mean FEV1 1.31 l increasing to 1.71 l after 200 micrograms salbutamol inhalation). 'Franol' produced dose-dependent bronchodilation. Two tablets caused significant bronchodilation from 90 minutes to 8 hours (peak change from baseline at 2.5 hours: FEV1 20.8%, PEFR 22.3%). One tablet of 'Franol' produced significant bronchodilation only between 60 minutes and 3 hours (change from baseline at 2.5 hours: FEV1 7.5%, PEFR 7.9%). There was no change in lung function with placebo (change from baseline at 2.5 hours: FEV1 5.4%, PEFR 5.9%). Median serum theophylline levels at 2.5 hours were 6.38 micrograms/ml for 2 tablets and 3.18 micrograms/ml for 1 tablet. Median peak phenobarbitone levels were 0.5 micrograms/ml. There were no clinically relevant changes in pulse rate and blood pressure during the study and no adverse events were reported.

Administration, Oral↗

Cationic neutrophil proteins increase transendothelial albumin movement.

Neutrophils play a role in the development of pulmonary edema in many models of the adult respiratory distress syndrome, but the mechanism of their action is not completely understood. We asked whether two neutrophil secretory products, human neutrophil cationic protein (NCP) and human neutrophil elastase (HNE), would nonenzymatically alter the movement of albumin across a cultured endothelial monolayer. Both enzymes were inactivated by heating before use. HNE was additionally enzymatically inactivated with a chloromethylketone oligopeptide (CMK) inhibitor and with alpha 1-proteinase inhibitor (alpha 1-PI). Heated NCP, heated HNE, and CMK-complexed HNE all increased transendothelial albumin transfer. The cation protamine also increased albumin transfer across the endothelium and this increase was blocked by heparin. Alpha 1-PI and fetal bovine serum also prevented the cationic proteins from increasing albumin transfer. Using the release of lactate dehydrogenase as a marker of cytotoxicity, heated HNE was toxic to endothelial cells, heated NCP had only minimal toxicity, and protamine had no toxicity. Changes in endothelial cell shape with gap formation was seen after exposure to both heated HNE and heated NCP. Both the cytotoxicity associated with heated HNE and the cell shape changes associated with heated NCP and heated HNE could be blocked by heparin. These results suggest that in addition to neutrophil proteases and reactive O2 molecules, neutrophil-derived cationic proteins can directly and nonenzymatically contribute to edema formation during acute inflammation.

Antimicrobial Cationic Peptides↗

The association of an elastase with amyloid fibrils.

The fibrils of all systemic forms of amyloid (primary, AL; secondary, AA; and hereditary, AF) that had been isolated by the water extraction procedure demonstrated elastolytic enzyme activity when examined in a specific assay using tritiated elastin. The source of this fibril-bound enzyme activity was consistent with human neutrophil elastase (HNE), since it was readily extracted by high salt solutions and inhibited by an elastase-specific chloromethyl ketone inhibitor, human alpha-1-protease inhibitor or by an antibody specific for HNE. The presence of an elastase on the amyloid fibril may suggest physiologic mechanisms of amyloid precursor protein degradation.

Amyloid↗

Relaxation techniques in general practice.

Many common disorders which present in general practice may be treated successfully when patients learn techniques of relaxation. Tension headache, migraine, chronic nervous diarrhoea, pre examination tension and some phobias have a high success rate. The technique is a lifelong asset for both patient and doctor.

Anxiety Disorders↗