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Biomedical subjects

C Ward

Publications and source records attributed to C Ward.

At least 181 records · Page 10Linked to original sources
PubMed1988

Protective effect of the bispiperazinedione ICRF-187 against doxorubicin-induced cardiac toxicity in women with advanced breast cancer.

Studies in animals suggest that the bispiperazinedione ICRF-187 can prevent the development of dose-related doxorubicin-induced cardiac toxicity. In a randomized trial in 92 women with advanced breast cancer, we compared treatment with fluorouracil, doxorubicin, and cyclophosphamide (FDC), given every 21 days, with the same regimen preceded by administration of ICRF-187 (FDC + ICRF-187). Patients were withdrawn from the study when cardiac toxicity developed or the cancer progressed. The mean cumulative dose of doxorubicin tolerated by patients withdrawn from study was 397.2 mg per square meter of body-surface area in the FDC group and 466.3 mg in the FDC + ICRF-187 group (no significant difference). Eleven patients on the FDC + ICRF-187 arm received cumulative doxorubicin doses above 600 mg per square meter, whereas one receiving FDC was able to remain in the study beyond this dose. Antitumor response rates were similar (FDC vs. FDC + ICRF-187, 3 vs. 4 complete responses; 17 vs. 17 partial responses; and 9.3 vs. 10.3 months to disease progression). Although myelosuppression was slightly greater in the FDC + ICRF-187 group, the incidence of fever, infections, alopecia, nausea and vomiting, or death due to toxicity did not differ between the groups. Cardiac toxicity was evaluated by clinical examination, determination of the left ventricular ejection fraction by multigated nuclear scans, and endomyocardial biopsy. In comparisons of the FDC group with the FDC + ICRF-187 group, clinical congestive heart failure was observed in 11 as compared with 2 patients; the mean decrease in the left ventricular ejection fraction was 7 vs. 1 percent when the cumulative dose of doxorubicin was 250 to 399 mg per square meter (P = 0.02), 16 vs. 1 percent at 400 to 499 mg (P = 0.001), and 16 vs. 3 percent at 500 to 599 mg (P = 0.003); and the Billingham biopsy score was 2 or more in 5 of 13 patients undergoing biopsy vs. none of 13 (P = 0.03). We conclude that ICRF-187 offers significant protection against cardiac toxicity caused by doxorubicin, without affecting the antitumor effect of doxorubicin or the incidence of noncardiac toxic reactions.

Adult↗
PubMed1988

Effects of lorazepam on memory, attention and sedation in man.

The effects of three doses of lorazepam (0.5, 1.0 and 2.0 mg PO) on various aspects of memory, attention and sedation are described. Lorazepam produced dose-related deficits in verbal secondary memory, choice reaction time and a novel vigilance task. It also produced a dose-dependent increase in subjective sedation, and an enhancement of visual contrast sensitivity. These results are compared with those reported earlier using the muscarinic antagonist scopolamine, and discussed in relation to models of Alzheimer's disease.

Adult↗
PubMed1988

Evaluation of a low to middle tar/medium nicotine cigarette designed to maintain nicotine delivery to the smoker.

A specific objective of this 6-week crossover study was to determine how 21 regular smokers of middle tar cigarettes changed their smoking behaviour and uptake of smoke constituents, when switching to either lower tar cigarettes capable of delivering amounts of nicotine similar to a conventional middle tar cigarette (maintained nicotine product), or to conventional low tar/low nicotine cigarettes. Subjects visited the laboratory every 2 weeks for detailed assessment of their smoking behaviour. Weekly per capita consumption was similar for all three cigarettes. They were smoked with variable intensities (low tar greater than maintained nicotine greater than middle tar), the tendency being for larger puff volumes, faster puffing and increased puff duration with the low tar cigarettes. The maintained nicotine cigarette was preferred to the middle tar cigarette, although acceptability ratings of the three cigarettes only differed marginally. The nicotine absorbed from the maintained nicotine and middle tar cigarettes was similar and significantly greater than the levels achieved from the low tar cigarettes. Intake of carbon monoxide into the mouth and absorption into the blood stream was lower for the maintained nicotine cigarette than for the middle tar cigarette, with the low tar cigarette occupying an intermediate position. Derived estimates of tar intake suggested reduced intake of tar into the respiratory tract (around 25%) from the maintained nicotine product relative to the middle tar product. The possible advantages of switching to maintained nicotine cigarettes is discussed.

Adult↗
PubMed1988

Modelling dementia: effects of scopolamine on memory and attention.

Scopolamine, a muscarinic cholinergic antagonist, is capable of inducing transient memory impairment in normal subjects. Against the background of the cholinergic hypothesis of Alzheimer's disease (AD) the present study was designed to investigate the effects of low oral doses of scopolamine on a range of cognitive functions known or hypothesized to be affected in AD. Twenty healthy volunteers (18-48 yr) performed a battery of automated cognitive tasks under each of five treatments: oral scopolamine 0.3 mg, 0.6 mg, 1.2 mg; oral methylscopolamine 0.6 mg; placebo. Alongside analogous tests of verbal and non-verbal memory, the battery enabled assessments of a range of attentional functions: alerting, sustained attention, selective attention, and covert orientation. A profile of effects was observed within and beyond the realm of memory. While some functions were unaffected by the drug (e.g. alerting) and others were impaired at the highest dose (e.g. verbal learning) still others were affected in a linear dose-dependent manner (sustained attention; visual contrast sensitivity). These observations are discussed in the context of the "scopolamine model" of AD.

Adolescent↗
PubMed1988

Reversal of histamine-induced bronchoconstriction by the H1-receptor antagonist levocabastine: a potential model for efficacy in anaphylaxis.

1. The rate of onset and magnitude of the effect of levocabastine, a potent H1-receptor antagonist, in reversing histamine-induced bronchoconstriction were determined in a double-blind cross-over trial against saline placebo. Histamine was administered by nebuliser so that forced expiratory volume in 1 second (FEV1) was reduced to 80-75% of baseline FEV1 in 10 men with mildly or moderately responsive airways and the effects of intravenous injection of saline or saline + 200 micrograms levocabastine were studied. 2. The maximum rate of recovery of FEV1 was 7[2-10]% min-1 (median [range]) in the first 5 min after levocabastine injection, but only 4[1-7]% min-1 after saline alone (P less than 0.05). 3. The median area under the recovery curve of FEV1 from 0 to 30 min after injection was 405 [228-498]% basal FEV1 X min after levocabastine and 301[98-502]% basal FEV1 X min after saline alone (P less than 0.002). 4. FEV1 returned to 90% of baseline within 30 min in all subjects after levocabastine, but not after saline alone (P less than 0.002). 5. Histamine-induced bronchoconstriction was relieved more quickly by levocabastine than saline alone. This model may have application to the study of drugs used in the treatment of anaphylaxis.

Adult↗
PubMed1988

Assessment of pulmonary macrophage and neutrophil function in sequential bronchoalveolar lavage aspirates in sarcoidosis.

Bronchoalveolar lavage was performed in eight patients with biopsy proved sarcoidosis and eight control subjects matched for age and smoking habit, three sequential 60 ml aliquots of sterile saline being used. Each aliquot was aspirated and analysed separately to determine total and differential cell counts. Cellular metabolic activity was stimulated with latex and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. In control subjects mean total cell counts were significantly greater in the second aspirate than in the first, but fell slightly in the third. Similarly, in the patients with sarcoidosis mean total cell counts increased from aspirate 1 to a maximum in aspirate 2, before falling again marginally in aspirate 3. The only significant difference in cell counts between patients with sarcoidosis and controls was an approximately threefold increase in total lymphocyte counts in the former in each of the three aspirates. Luminol chemiluminescence was similar in patients with sarcoidosis to that in controls in the first aspirate, but was significantly greater in the second and third aspirates. Lucigenin chemiluminescence was also significantly greater in the second and third aspirates only. Thus in patients with sarcoidosis lymphocyte numbers are increased in all three aspirates whereas cellular metabolic activity is increased to a greater extent in later aspirates, which may reflect events occurring in the periphery of the lung segment.

Acridines↗
PubMed1988

Number and activity of inflammatory cells in bronchoalveolar lavage fluid in asthma and their relation to airway responsiveness.

Bronchial responsiveness to inhaled methacholine was measured four to six days before fibreoptic bronchoscopy in 22 asthmatic patients (10 smokers) and 20 control subjects (12 smokers). The asthmatic patients had a baseline FEV1 greater than 60% predicted and a PD20FEV1 (provocative dose of methacholine causing a 20% fall in FEV1) of 0.006-3.7 mg. The 20 control subjects had normal pulmonary function and a PD20FEV1 above the maximum cumulative dose of methacholine of 6.4 mg. Bronchoalveolar lavage of a middle lobe segment (lingula in four subjects) was performed with three sequential 60 ml aliquots of sterile saline. Cellular metabolic activity was stimulated with latex in aliquots of resuspended cells, and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. Mean absolute total cell counts were similar in the asthmatic and control groups but there were differences in differential cell counts, with a significant increase in eosinophil (p less than 0.05) and lymphocyte (p less than 0.005) counts in asthma. PD20FEV1 was negatively correlated with percentage neutrophil counts (p less than 0.005). Luminol enhanced chemiluminescence/1000 neutrophils was increased about twofold in asthmatic subjects (p less than 0.001), but was not correlated with PD20FEV1 Lucigenin enhanced chemiluminescence/1000 macrophages was increased nearly fourfold in asthmatic patients (p less than 0.001) and showed a negative correlation with PD20FEV1 (p less than 0.01). The macrophage count was increased twofold in current smokers in both groups, but other cell numbers were not altered significantly. Smoking did not affect cellular metabolic activity in either group. This study supports the idea that an inflammatory process is present in the airways of those with asthma, and suggests a relation between bronchial responsiveness and both neutrophil numbers and macrophage activity.

Adolescent↗
PubMed1987

In vitro methylation of the 5'-flanking regions of the mouse beta-globin gene.

The enzymatic methylation of the 5'-flanking region of the mouse beta-globin (major) gene containing putative regulatory regions has been investigated. In vitro methylation of this 368-base pair regulatory DNA by a DNA methyltransferase obtained from mouse erythroleukemia cells yields an asymmetric methylation pattern. Of the 10 available CG pairs, only 5-6 are modified, leading to one hemimethylated site and two apparently fully methylated sites. Only CG pairs which are localized in a 29-base pair cluster are methylated. The data suggest that a CG cluster approximately 100 base pairs upstream from the CAP site may be the in vivo site of methylation in the 5'-regulator region of the mouse beta-globin gene.

Animals↗
PubMed1987

Exertional gastro-oesophageal reflux: a mechanism for symptoms in patients with angina pectoris and normal coronary angiograms.

During 24 hour oesophageal pH monitoring 52 patients who had angina pectoris and normal coronary angiograms underwent exercise testing, as far as their symptoms allowed, on a treadmill to determine whether gastro-oesophageal reflux occurred during exertion. In 11 patients the 24 hour oesophageal pH score was abnormally high; 10 of these showed exertional gastro-oesophageal reflux, and in nine this was associated with their usual chest pain. A further 13 patients had a normal 24 hour pH score but had exertional reflux coincident with chest pain during exercise testing. The mean lower oesophageal sphincter pressure in both of these groups of patients was appreciably lower than that in 28 patients who had a normal 24 hour pH score and no exertional reflux. These findings suggest that exertional gastro-oesophageal reflux accounts for the symptoms of a large proportion of patients who have angina pectoris and normal coronary angiograms and that oesophageal pH monitoring during exercise testing on a treadmill enables this group of patients to be identified.

Adult↗
PubMed1987

A controlled trial of nebulized aminoglycoside and oral flucloxacillin versus placebo in the outpatient management of children with cystic fibrosis.

Six children with cystic fibrosis who had persistently had Pseudomonas aeruginosa isolated from their respiratory tract, completed a double-blind cross-over comparison of oral flucloxacillin and nebulized aminoglycoside versus double placebo. The patients had higher FEV1 results at the end of the month of active treatment than after the month of placebo.

Administration, Inhalation↗
PubMed1987

Cardiac lymphoma: an unusual case of myocardial perforation--clinical, echocardiographic, haemodynamic and pathological features.

A patient is described in whom lymphoma infiltrated the pericardium and myocardium resulting in right ventricular rupture. Pericardial blood and lymphoma deposit were demonstrated echocardiographically as echolucent and echodense areas respectively and confirmed at autopsy. The patient presented with the clinical and haemodynamic features of cardiac tamponade.

Cardiac Tamponade↗
PubMed1987

Left ventricular function and oesophageal function in patients with angina pectoris and normal coronary angiograms.

Left ventricular function and oesophageal function (including oesophageal manometry and pH monitoring) were investigated and a psychiatric assessment carried out in 63 patients with angina pectoris and normal coronary angiograms. Twenty two (35%) patients had regional abnormalities of left ventricular wall motion (group A). Thirty six (57%) patients had an oesophageal abnormality (group B); 19 patients had gastro-oesophageal reflux and abnormal oesophageal motility, five had gastro-oesophageal reflux alone, and 12 had abnormal oesophageal motility alone. Only four had regional abnormalities of the left ventricular wall and abnormal oesophageal function. In nine (14%) patients left ventricular and oesophageal function were normal (group C). Psychiatric morbidity was significantly less common in group A than in groups B and C and was similar in group B and group C. A definite abnormality of left ventricular function, oesophageal function, or psychiatric morbidity is present in a high proportion of patients with angina pectoris and normal coronary angiograms and in some instances this may lead to specific treatment. If quantitative assessment of left ventricular function is normal, oesophageal investigations should be performed. Endoscopy of the upper gastrointestinal tract may demonstrate oesophageal disease, but, if findings are normal, oesophageal manometry and ambulatory oesophageal pH monitoring (including during treadmill exercise testing) should be carried out.

Adult↗
PubMed1987

Anatomical distribution of bronchoalveolar lavage fluid as assessed by digital subtraction radiography.

A digital subtraction imaging technique was used to visualise directly the anatomical distribution of 3 X 60 ml aliquots of saline containing a low concentration of radio-opaque dye, introduced sequentially into a segment of the middle lobe. It was possible to estimate the relative movement of fluid within the segment during the sequential aspiration of each of these aliquots. The first 60 ml aliquot introduced stayed close to the bronchoscope and probably sampled only the proximal airways. With the introduction of cumulative volumes of 120 ml or more, the fluid filled the segment more evenly. Aspiration then moved fluid back from the periphery, implying that the aspirate had also lavaged both distal airways and alveoli.

Adult↗
PubMed1987

Surgical repair of acquired ventricular septal defect. Determinants of early and late outcome.

Between January 1970 and June 1985, 60 patients underwent surgical repair of postinfarction ventricular septal defect. The preoperative cineangiograms of all patients were reviewed to measure left ventricular ejection fraction and to quantitatively assess right ventricular function by measuring the percentage reduction in right ventricular midcavity diameter. There were 23 early deaths (within 30 days) and 14 late deaths occurring between 1 and 92 months after operation. Of the 23 long-term survivors, 87% are in New York Heart Association Class I or II. The early mortality was significantly higher for inferior infarction (58%) than for anterior infarction (25%). Early mortality was also influenced by the time interval between infarction and operation (under 1 week 41%, over 4 weeks 22%). Early survival was favored by good preoperative right ventricular function; the percentage reduction in right ventricular midcavity diameter was 16.5% +/- 9.5% (mean +/- standard deviation) for the early death group and 26.7% +/- 10.6% for the early survival group. However, the early outcome was not influenced by left ventricular function before operation. Conversely, long-term survival was favored by preserved preoperative left ventricular function; left ventricular ejection fraction was 26.2% +/- 9.3% for the late death group and 35% +/- 8.5% for the late survival group. Long-term survival was not, however, affected by right ventricular function before operation. The results of surgical closure of postinfarction ventricular septal defect have improved between two successive time frames in this series, which is the largest to date.

Aged↗