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Biomedical subjects

A Noseda

Publications and source records attributed to A Noseda.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1987

Acute pancreatitis as presenting symptom and sole manifestation of small cell lung carcinoma.

A 58-year-old man with no sign of pulmonary disease and a normal chest x-ray presented with acute pancreatitis resistant to conventional medical management and a mass in the head of the pancreas. The presumptive diagnosis was pancreatic cancer with tumor-induced pancreatitis. However, endoscopic retrograde cholangiopancreatography suggested metastatic rather than primary tumor, so that an extrapancreatic primary was actively sought. Further lung work-up demonstrated a small cell carcinoma of the lung. This case indicates that metastasis-induced acute pancreatitis can be the presenting symptom and sole manifestation of lung cancer.

Acute Disease↗
PubMed1987

Neoplastic cell inhibition with new ether lipid analogs.

Bioactive phospholipid analogs of platelet-activating factor (PAF) represent a new approach to cancer chemotherapy. Various modifications of the basic structure of PAF lead to different ether lipid (EL) analogs. Data from the evaluation of thioalkyl and amidoalkyl glycerophosphocholine and of glycerophosphoinositol EL analogs against different experimental tumors in vitro (HL60 and K562 human leukemia cells, BG1 and BG3 ovarian adenocarcinomas) are presented. Exclusion of trypan blue after short exposure to the drugs determined cytotoxicity, and a soft agarose clonogenic assay measured the ability of the analogs to inhibit tumor cell proliferation. The thioalkyl EL are very active against the cell lines using both end points, and the amidoalkyl EL showed efficacy against the leukemic cell lines, whereas the phosphoinositol EL are active only at high concentrations. Combined use of EL analogs, which are membrane-interactive, with classical DNA-interactive chemotherapeutic drugs revealed that the combinations have additive antiproliferative effects. These results are promising leads in the development of the anticancer potential of ether lipid analogs.

Antineoplastic Agents↗
PubMed1987

Increased plasma motilin concentrations in small cell carcinoma of the lung.

Plasma samples from 21 patients with small cell carcinoma of the lung were screened for pancreatic polypeptide, somatostatin, motilin, and vasoactive intestinal polypeptide. One patient had severe impairment of both renal and liver function. In the 20 remaining subjects vasoactive intestinal polypeptide concentrations were normal, and only two patients had increased concentrations of somatostatin. Increases in pancreatic polypeptide were detected more commonly (7/20), but these may have been non-specific age related increases. The major finding was high concentrations of motilin (greater than 496 pg/ml) in 17 of 20 patients. Plasma motilin was subsequently assayed in 16 more patients with lung cancer, including 10 patients with non-small cell carcinoma of the lung. At concentrations over 900 pg/ml plasma motilin appears to be a tumour marker for small cell carcinoma of the lung with acceptable sensitivity (59%) and specificity (78%). The origin of increased plasma motilin in small cell carcinoma of the lung was investigated. Bombesin (gastrin releasing peptide), a peptide known to stimulate the release of motilin in man, was, as in previous studies, detected in tumour but not in plasma, except in one patient out of 21. Immunohistochemical studies failed to detect motilin antigen in biopsy samples. Motilin tumour content was found to be low in tumour tissue from three patients with small cell carcinoma of the lung who had appreciable hypermotilinaemia and from three patients with non-small cell carcinoma of the lung who had either normal or slightly raised plasma motilin concentrations. The stimulus to motilin secretion in patients with small cell carcinoma of the lung remains unclear.

Adult↗
PubMed1985

[Nocardia infection: diagnostic and therapeutic problems. 9 cases].

Nocardia asteroides was isolated in 9 patients between June 1982 and February 1984. Clinical manifestations included acute pneumonia (3 cases), chronic lung abscess (2 cases, one of them requiring exploratory thoracotomy) and relapsing infection of the lacrimal canaliculus (1 case). Sputum or bronchial secretions were positive in 3 other patients without evidence of pneumonia, which could represent either an asymptomatic carrier state or a mild bronchial infection. Seven patients had one or several conditions known to favour Nocardia infection, the most frequent being steroid therapy (4 cases), while 2 patients had no predisposing factor. In our series of 5 nocardial lung infections, 2 patients had positive blood cultures. This quite unusually high rate may be related to the use of diphasic bottles and to our systematic policy of prolonged examination of blood cultures taken from immunocompromised patients. Cotrimoxazole was used as the first choice antinocardial agent.

Aged↗
PubMed1985

Trisomy 11 in preleukemia.

The clinical and cytogenetic findings of a patient with a preleukemic state and trisomy 11 are reported. Trisomy 11 was present as the sole karyotypic alteration at the time of overt leukemia. Trisomy 11 presents an additional chromosomal abnormality not previously described in preleukemia.

Bone Marrow↗
PubMed1985

Lung function in children and adolescents with antecedents of acute rheumatic fever.

Static lung volumes, CO-lung transfer, airway resistance, maximal expiratory flows and lung elastic properties were studied in 29 children and adolescents 1-10 years after recovery from acute rheumatic fever. There were essentially no changes in lung function even in the subjects with a residual valvular disease. The only abnormality was a tendency for the elastic lung recoil at TLC to be low, which is interpreted as probably reflecting a decrease in inspiratory muscle force.

Acute Disease↗
PubMed1985

Prostaglandins and aminoglycoside nephrotoxicity.

The role of prostaglandins in the development of aminoglycoside-induced acute renal failure was studied in CD-COBS rats (200 to 250 g). The animals were treated with gentamicin (80 mg/kg), acetylsalicylic acid (ASA, 100 or 200 mg/kg), or both drugs or saline for 5 or 10 days. Renal function was studied measuring creatinine clearance, blood urea nitrogen (BUN), and serum electrolytes, urine osmolality, and maximal urinary concentrating capacity after water deprivation and vasopressin administration. Gentamicin toxicity on the proximal tubule was evaluated by measuring urinary excretion of the lysosomal enzyme N-acetylglucosaminidase (NAG). Renal prostaglandin (PG) production was evaluated measuring the concentration of PGE2, PGD2, PGF2 alpha, 6-keto-PGF1 alpha, and thromboxane B2 (TXB2) in whole renal homogenate after a 15-min incubation at 37 degrees C using gas chromatography-mass spectrometry. Gentamicin alone reduced the glomerular filtration rate (GFR) 20 to 30% after 5 and 10 days of treatment. Combination with ASA potentiated the toxic effect of the aminoglycoside after 10 but not after 5 days of treatment. Similarly, gentamicin reduced the urinary concentrating capacity and addition of ASA worsened the effects. Gentamicin markedly increased NAG excretion but this effect was reduced by ASA, probably as a result of lysosomal stabilization. ASA alone inhibited the production of prostaglandins in renal tissue by 70 to 90% after single or multiple doses. The animals treated with gentamicin alone presented a significant, specific increase in PGE2 production after 10 days of treatment but this increase did not occur when the two compounds were given together. Since PGE2 has a vasodilatory effect in the kidney these results suggest that it may play a specific role in maintaining normal renal blood flow and GFR during the development of aminoglycoside nephrotoxicity. The inhibition of prostaglandin production by nonsteroid anti-inflammatory drugs prevents this compensatory mechanism and worsens the renal damage.

Analysis of Variance↗