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Biomedical subjects

A Noseda

Publications and source records attributed to A Noseda.

At least 19 recordsLinked to original sources
PubMed1992

Dyspnoea assessed by visual analogue scale in patients with chronic obstructive lung disease during progressive and high intensity exercise.

BACKGROUND: A study was carried out to determine whether rating of dyspnoea by means of a visual analogue scale during a progressive exercise test is affected by the subject's awareness of the progressive nature of the protocol. METHODS: Nineteen patients with chronic obstructive lung disease (FEV1 mean (SE) 1.06 (0.07) 1) were studied. A preliminary incremental test was carried out with a work rate increasing by 10 watts every minute until the subject could no longer exercise, to determine the maximum work load (Wmax) and to anchor the upper end of the visual analogue scale. This was followed by two exercise tests performed one day apart in randomised sequence, with two different protocols. One was a 12 minute protocol that included two sudden bursts of three minute high intensity exercise, up to the subject's Wmax, each preceded by three minutes of low level exercise. The other test was a conventional three minute incremental test lasting 12 minutes. On both study days the only information given to the subject about the temporal profile of load was that a change would be made every three minutes. The relation between dyspnoea, as assessed by the visual analogue scale, and ventilation, measured during high intensity or progressive exercise, was studied. RESULTS: The mean (SE) rates of increase of dyspnoea with increasing ventilation (% of line length 1(-1) min) obtained by linear regression analysis were similar for the two tests (2.86 (0.20) for progressive exercise and 2.87 (0.25) for high intensity exercise); it was 2.59 (0.25) for the initial burst of high intensity exercise when the data on this were analysed separately. In six subjects with stable disease studied again two months later the reproducibility of the rating of dyspnoea was reasonably good for both protocols. CONCLUSION: The results suggest that in most patients with chronic obstructive lung disease the assessment of exercise induced dyspnoea by means of a visual analogue scale during a progressive exercise test is not affected by the subject's awareness of the progressive increase in work intensity.

Awareness↗
PubMed1992

Perceived effect on shortness of breath of an acute inhalation of saline or terbutaline: variability and sensitivity of a visual analogue scale in patients with asthma or COPD.

The purpose of the study was to validate a bipolar visual analogue scale (VAS) to assess the perceived effect on shortness of breath of an acute inhalation and to search for differences in perception between asthmatics and subjects with chronic obstructive pulmonary disease (COPD). Thirty two subjects with airway obstruction and a diagnosis of either asthma (n = 16) or COPD (n = 16) received three consecutive inhalations of isotonic saline, followed by two inhalations of 400 micrograms terbutaline. Saline was perceived by asthmatics as a slight improvement: VAS (median, 95% confidence interval) 9%, 0-18% of line length. COPD subjects could be separated into two subgroups: "high perceivers" (n = 8, VAS 43%, 33-53%) and "low perceivers" (n = 8, VAS 5%, 3-7%). The median intrasubject coefficient of variation of the three post-saline VAS ratings was 19.4% (asthma), 12.5% (COPD high perceivers), and 14.5% (COPD low perceivers). After terbutaline, asthmatics had, by selection, a larger increase in forced expiratory volume in one second (FEV1) than COPD subjects. However, for other indices (expiratory specific resistance, inspiratory vital capacity and maximal inspiratory flow at 50% forced vital capacity) the changes were smaller in COPD low perceivers than in both asthmatics and COPD high perceivers. The parallel improvement in VAS was 24%, 20-39% (asthma), 15%, 6-25% (COPD high perceivers) and 1%, -1-8% (COPD low perceivers). The most sensitive index was FEV1 in asthmatics, vital capacity in COPD subjects, VAS being among the most sensitive indices in the former, but among the least sensitive in the latter. We conclude that the sensitivity of this VAS to bronchodilation is better in asthmatics than in COPD subjects. The latter can however be separated into subgroups with high and low level of perception.

Asthma↗
PubMed1991

Increased ether lipid cytotoxicity by reducing membrane cholesterol content.

Ether-linked glycerophospholipids (ether lipids, EL) are selectively toxic and anti-proliferative agents against cancer cells in vitro. The reason for such selectivity is not completely clear. Their mechanism of action is mediated through an interaction with the plasma membrane and the membrane lipid composition may modulate it. As a continuation of previous reports, we now present data showing that cholesterol concentration modulates EL toxicity in the K562, U937 and MOLT4 leukemic cell lines in vitro. Cells become sensitive to otherwise ineffective doses of EL when their cholesterol content is lowered. Cell cholesterol levels were reduced by exposure to an egg lipid mixture (neutral glycerides, phosphatidylcholine and phosphatidylethanolamine, AL721). The data contribute to an understanding of the EL mechanism of action on membranes and suggest that the cellular cholesterol concentration must be considered a major factor in modulating the cytotoxic effects of EL.

Cholesterol↗
PubMed1990

Role of cell cholesterol in modulating antineoplastic ether lipid uptake, membrane effects and cytotoxicity.

Membrane-interactive ether lipids (EL) exert toxic and antiproliferative effects on cancer cells in vitro. They appear to be selectively more toxic to cancer cells than to normal cells and thus they are ideal candidates for bone-marrow purging procedures. However, no conclusive explanation has yet been provided for this property. We now present some data indicating that the cholesterol concentration in the incubation medium modulates EL toxicity against the HL60 leukemic cell line in vitro. Furthermore, model membranes richer in cholesterol take up EL more slowly, and cell cholesterol enrichment of HL60 cells counteracts EL biophysical membrane interaction, but not toxicity, in our experimental model. However, the K562 cell line, a leukemia line less sensitive to EL toxic action, has higher levels of cell cholesterol. Our data provide evidence to explain differences in sensitivity to EL among different cell types and contribute to the understanding of the mechanism of action of EL.

Antineoplastic Agents↗
PubMed1990

Cross-resistance pattern of cell lines selected for resistance towards different cytotoxic drugs to membrane-toxic phospholipids in vitro.

The synthetic ether lipids ET-18-OCH3 and BM41.440 and a derivative, hexadecylphosphocholine, were tested for inhibition of [3H]-thymidine uptake into a Chinese hamster ovarian cell line (AUXBl) and its multidrug-resistant subline selected for colchicine resistance (CHRC5). The activity of all three compounds against the multidrug-resistant subline was equal to or higher than that against the parent line. The same result was found for their activity against a human leukemic lymphoblastic cell line (CEM/O) and its methotrexate-resistant subline (CEM/MTX). In contrast, two multidrug-resistant cell lines selected for resistance to Adriamycin, the mouse leukemia cell line P388/ADR and the murine sarcoma cell line S180/ADR, expressed modest cross-resistance to the lipids as measured by thymidine uptake. Experiments performed using the trypan-blue dye-exclusion assay yielded comparable results, although this system revealed a slightly different sensitivity in showing the cytotoxicity of the drugs. By this assay, modest cross-resistance for ET-18-OCH3 and BM41.440 to Adriamycin was found only after 24 h incubation and decreased after 48 h incubation, with almost equal sensitivity to both drugs being shown by the parental (P388/W) and resistant lines (P388/ADR). Furthermore, findings from a human tumor-cloning assay were in accordance with these data, although they did not indicate cross-resistance for the P388/ADR cell line. These results suggest that certain ether lipids and derivatives might represent valuable anticancer drugs warranting further study in the setting of resistant disease.

Animals↗
PubMed1989

[Left ventricular function in obstructive chronic bronchopneumopathy].

Left ventricular (LV) function was studied, using echocardiography, radionuclide angiography and right catheterization, in 20 patients (mean age 60.9 +/- 1.5 years) with severe stable chronic obstructive pulmonary disease (COPD) and without known heart disease. The diagnosis of LV failure, suspected on clinical grounds in 8 of these patients, was confirmed by raised pulmonary capillary wedge pressure (PCWP) in only one patient. Nineteen subjects had normal PCWP and LV ejection fraction (LVEF) values, radionuclide LVEF and end diastolic LV dimension being the most powerful discriminators between the single abnormal patient and the others. Echocardiograms of sufficient quality were obtained in 11 out of the 19 normal patients and constantly showed LV dimensions in the lowest part of the normal range. The stroke volume index (SVI) - cardiac output being measured by thermodilution - was found to be decreased in 9 of 14 patients with normal LVEF values. We conclude that in patients with severe COPD (1) LV failure is quite unfrequent and the empirical use of digitalis should not be recommended, (2) radionuclide angiography is the most useful procedure for routine evaluation of LV function and (3) a decreased SVI is frequently found in patients with a small LV cavity and a normal LVEF, suggesting some degree of diastolic dysfunction of the left ventricle.

Blood Volume Determination↗
PubMed1989

Lung function, maximum and submaximum exercise testing in COPD patients: reproducibility over a long interval.

This study was designed to investigate the reproducibility and clinical relevance of several lung function and exercise test indices in a sample of patients with stable severe chronic obstructive pulmonary disease (COPD). Twenty subjects (ages 67.8 +/- 2.0 years, forced expiratory volume in 1s, [FEV1] 39.7 +/- 2.8% predicted) receiving conventional medical therapy and pulmonary rehabilitation were tested 4 times at 1 month intervals. Testing procedures included lung function (inspiratory vital capacity [IVC], FEV1, plethysmographic functional residual capacity [FRC], specific conductance of the airways (sGaw), single breath transfer factor divided by the alveolar volume [TL/VA]); incremental, progressive, symptom-limited, cycle exercise (maximum work load [Wmax], maximum heart rate [HRmax], maximum ventilation [VEmax], maximum oxygen uptake [VO2max]); and 2 modes of submaximum exercise (12 min walking test [12 MWD] and endurance cycle test). The mean of the absolute value of the individual patient, session-to-session, variation was found to be 0.131 for FEV1, 102 ml/min for VO2max. The within-subject variability was the smallest for HRmax and IVC (mean intrasubject coefficient of variation, [CV intra] 5.0 and 6.5%) and the greatest for TL/VA, the work performed during the endurance cycle test (EW) and sGaw (CV intra 16.5, 19.4, and 22.7%), while it was reasonably low (8.1-10.2%) for all the other variables studied. Calculation of the F ratio of the intersubject variance to the residual (total minus intersubject) variance, interpreted as a signal-to-noise, ratio, yielded the following, in decreasing order: TL/VA, EW, VEmax, VO2max, IVC, FEV1, HRmax, Wmax, sGaw, 12 MWD, FRC. If we assume that a useful variable should combine a low within-subject variability (CV intra less than or equal to 10%) with a high signal-to-noise ratio, we conclude that, among all the variables studied, IVC, FEV1, VEmax, and VO2max are those with the greatest clinical potential for functional assessment in patients with COPD.

Aged↗
PubMed1989

Membrane damage in leukemic cells induced by ether and ester lipids: an electron microscopic study.

This paper reports a scanning electron microscopy (SEM) study of different leukemic cell lines exposed to 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe). This is an ether lipid analog of platelet activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) which inhibits neoplastic cell growth in vitro and in vivo and is believed to exert its action through an interaction with the plasma membrane. In this paper evidence of the morphological alteration of leukemic cell membranes due to the exposure to varying concentrations of ET-18-OMe in vitro and in vivo is presented. This membrane damage consists of formation of blebs and holes, and the severity of these two phenomena correlate with the degree of cell viability loss. These alterations were analyzed in comparison to those induced by the known and structurally related permeabilizing agent, lysophosphatidylcholine, an ester lipid.

Animals↗
PubMed1989

Synthesis and biological evaluation of ether-linked derivatives of phosphatidylinositol.

The synthesis of two novel glycero-3-phosphoinositol ether lipid analogues, rac-1-O-octadecyl-2-O-methylglycero-3-phospho-myo-inositol 6 (an ether lipid analogue of rac-1-O-octadecyl-2-O-methylglycero-3-phosphocholine; ET-18-OMe) and rac-1-O-octadecyl-2-O-acetylglycero-3-phospho-myo-inositol 11 (an ether lipid analogue of platelet-activating factor), is described. The two target compounds and the synthetic intermediates were evaluated for inhibition of HL60, BG1, and BG3 human malignant cells in vitro and inhibition of protein kinase C. Tumor inhibitory activity was found for compounds 6 and 11 in all systems but not for their synthetic intermediates. However, compounds 6 and 11 as well as the synthetic intermediates 5 and 13, but not 9, exhibited protein kinase C inhibitory activity.

Chemical Phenomena↗
PubMed1989

Sympathomimetics in acute severe asthma: inhaled or parenteral, nebulizer or spacer?

It is accepted today that all patients with acute asthma should be treated with a sympathomimetic, irrespective of previous therapy. This short review addresses the question of the optimal mode of administration of these drugs in acute severe asthma. Inhaled sympathomimetics are as effective as subcutaneous adrenaline, or intravenous salbutamol or terbutaline, and, as they produce fewer side-effects, are recommended as the best mode of administration. However, self-medication with a ready to use subcutaneous preparation may be indicated in those patients prone to very abrupt attacks. The conventional mode of inhalation therapy in acute asthma is nebulization, but equally effective bronchodilatation may be obtained with metered-dose inhalers combined with valved spacers. Tachypnoeic patients unable to perform a conventional inhalation manoeuvre can use one-way valve inhalation devices with repeated tidal breaths. Finally, sequential or even continuous inhalation techniques have recently been advocated, particularly in patients with impending respiratory failure.

Administration, Inhalation↗
PubMed1989

[Sleep apnea syndrome : multidisciplinary management. Apropos of a preliminary experience].

The authors describe a multidisciplinary approach for patients with sleep apnea syndrome. During the first year 40 patients with obstructive sleep apnea documented by polysomnographic recordings were managed. Therapy proposed to the patient included weight loss and abstention from sedatives at night as sole treatment (n = 12) or, more often, combined with nasal and/or throat surgery (n = 21) or nasal continuous positive airway pressure (NCPAP) during sleep (n = 7). NCPAP was by far the most effective in reversing apneas but in view of its cost for the patient and its constraining aspects was proposed solely to those patients with the most severe apnea syndromes.

Adult↗
PubMed1988

Effects of antineoplastic ether lipids on model and biological membranes.

Differential scanning calorimetry and electron spin resonance were utilized to measure the effects of di-ether glycerophospholipid analogs (EL) on the physical properties of model membranes and on the membrane fluidity of HL60 leukemic cells. 1-Octadecyl-2-methyl-rac-glycero-3-phosphocholine (ET-18-OMe) and 1-thiohexadecyl-2-ethyl-rac-glycero-3-phosphocholine (ET-16S-OEt) lower the transition temperature of dimyristoylphosphatidylcholine vesicles in a range of concentrations between 0.5 and 15 mol %. Studies conducted on the interaction of EL with a wide spectrum of different phospholipids, namely dipalmitoylphosphatidylcholine, 1-hexadecyl-2-palmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, and dielaidoylphosphatidylethanolamine confirmed the ability of EL to effect the physical properties of model membranes. Changes in calorimetric enthalpy were observed only with phosphatidylethanolamine-containing phospholipids. ET-18-OMe and ET-16S-OEt increased the membrane fluidity of HL60 leukemic cells labeled with the fatty acid spin label probe 5-nitroxystearate. These data demonstrate the ability of EL to partition into phospholipidic domains and to change their physical properties. Furthermore, they affect the membrane fluidity of whole cells. These effects indicate an interaction between EL and the plasma membrane which may be of importance in determining the cytotoxic activity against tumor cells exerted by EL.

Antineoplastic Agents↗
PubMed1988

In vitro antiproliferative activity of combinations of ether lipid analogues and DNA-interactive agents against human tumor cells.

Ether lipid analogues of platelet-activating factor (1-octadecyl-2-acetyl-sn-glycero-3-phosphocholine) possess a wide range of biological activities, including inhibition of neoplastic cell growth in vitro and in vivo. This activity is believed to be membrane mediated. Three different ether lipid analogues, 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine, 1-thiohexadecyl-2-ethyl-rac-glycero-3-phosphocholine, and 4-amino-methyl-1-[2,3-(di-n-decyloxy)-n-propyl]-4-phenylpiperidine , were combined with three DNA-interactive drugs, Adriamycin, 4-hydroperoxycyclophosphamide, and cisplatin, in the expectation that combinations of drugs with different mechanisms of action might show enhanced antitumor activity. The in vitro antiproliferative activity of the combinations was measured with a semisoft agarose clonogenic assay of an ovarian adenocarcinoma cell line. Various permutations of drug combinations were studied. Isobologram analyses and different treatment schedules were performed. Enhanced antiproliferative activity was found with combinations of ether lipids with DNA-interactive drugs in comparison with single agents. Statistical evaluation of the data indicated that the increase in activity was due to an additivity phenomenon. Neither synergism nor antagonism was found.

Adenocarcinoma↗
PubMed1988

Synthesis and evaluation of neoplastic cell growth inhibition of 1-N-alkylamide analogues of glycero-3-phosphocholine.

Previously unreported analogues of the synthetic antitumor phospholipid ET-18-OMe (1-octadecyl-2-methoxy-rac-glycero-3-phosphocholine), in which the 1-ether oxygen has been replaced by an amido group, have been prepared and evaluated for in vitro cytotoxic effects and for inhibition of protein kinase C. The title compounds exhibit cytotoxic effects against several tumor cell lines and are approximately equipotent to ET-18-OMe. The compounds were also found to inhibit protein kinase C in an in vitro assay. This work is a continuation of our previous structure-activity studies on thio-substituted derivatives of ET-18-OMe.

Amides↗