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Biomedical subjects

M Milanese

Publications and source records attributed to M Milanese.

34 records · Page 2Linked to original sources
PubMed2000

Modulation of airway caliber by deep inhalation in children.

To elucidate whether deep inhalation (DI) modulates changes in airway caliber in childhood, we measured the effect of DI on respiratory impedance before and after inhaled methacholine or salbutamol in 4- to 7-yr-old children (n = 15) suffering from recurrent wheezing. In all children, the real part of impedance between 12 and 16 Hz (Re[Z](12-16)) increased after methacholine from 5.6 +/- 1.2 to 8.2 +/- 1.6 cmH(2)O. l(-1). s (P < 0.001) and resonance frequency from 18 +/- 3 to 25 +/- 5 Hz (P < 0.001). These changes were partially reversed by DI: Re[Z](12-16) decreased to 7.2 +/- 1.2 cmH(2)O. l(-1). s (P < 0.01) and resonance frequency to 19 +/- 5 Hz (P < 0.001). In nine children, on a separate occasion, Re[Z](12-16) decreased after salbutamol from 8.3 +/- 1.9 to 5.1 +/- 0.9 cmH(2)O. l(-1). s (P < 0.001) and resonance frequency from 21 +/- 6 to 15 +/- 3 Hz (P < 0.05). The decrease of Re[Z](12-16) was partially reversed by DI (to 6.2 +/- 1.4 cmH(2)O. l(-1). s, P < 0. 01), but resonance frequency did not change significantly (P = 0.75). We conclude that in 4- to 7-yr-old children pharmacologically induced changes in airway caliber are modulated by DI. These findings suggest that airway-to-parenchyma interdependence is operative in this age range.

Airway Resistance↗
PubMed1999

Activation of monoamine oxidase type-B by aluminum in rat brain homogenate.

Monoamine oxidase type B (MAO-B) activity is elevated in certain neurological diseases such as Alzheimer's and Parkinson's disease with respect to age-matched controls; the cause of this elevation is unknown. The documented accumulation of aluminum in certain neurodegenerative diseases prompted us to test the effect of Al3+ on the activity of MAO-B in rat brain homogenate. Results showed that the metal ion significantly increased MAO-B enzymatic activity in a dose-dependent manner, yielding a K(M) of 5.69 microM compared with 34.45 microM in the absence of the metal ion. The Vmax of 45.34 micromol/min was unchanged in the presence of the metal ion.

Aluminum↗
PubMed1999

Are most ICU infections really nosocomial? A prospective observational cohort study in mechanically ventilated patients.

A prospective cohort study was undertaken with two end points: (i) to compare the 48 h time cut-off with the carrier state criterion for classifying infections, and (ii) to determine a time cut-off more in line with the carrier state concept. All patients admitted to the intensive care unit and expected to require mechanical ventilation for a period > or = 3 days were enrolled. Surveillance cultures of throat and rectum were obtained on admission and thereafter twice weekly to distinguish micro-organisms that were imported into the intensive care unit from those acquired during the stay in the unit. A total of 117 patients with median age of 61 years and median Simplified Acute Physiology Score II of 42, were included in the study. Of these patients, 48 (41%) developed a total of 74 infection episodes. Using the 48 h cut-off point, 80% of all infections were classified as ICU-acquired. According to the carrier state criterion, 44 infections (60%) were of primary endogenous development caused by micro-organisms imported into the intensive care unit. Seventeen secondary endogenous (23%) and 13 exogenous (17%) infections were caused by bacteria acquired in the unit. The carrier state classification allowed the transfer of 49% of infections from the ICU-acquired group into the import group. A time cut-off of nine days was found to identify ICU-acquired infections better than two days. These data suggest that monitoring of carriage of micro-organisms may be a more realistic approach to classify infections developing in the intensive care unit.

Adult↗
PubMed1998

Anti-inflammatory agents and allergen-induced beta2-receptor dysfunction in isolated human bronchi.

Antigen challenge causes beta2-adrenoceptor dysfunction in sensitized human bronchi (Am. J. Respir. Crit. Care Med. 1997;155:1230-1234). This study investigated whether the dysfunction can be prevented by anti-inflammatory agents. Human bronchial rings (2 to 4 mm) from surgery were passively sensitized to house dust mite and challenged (1) with allergen only, (2) with allergen plus indomethacin (10(-)5 M), (3) with allergen plus nedocromil sodium (10(-)7 M to 10(-)5 M), (4) with allergen plus the H1-receptor antagonist cetirizine (10(-)7 M to 10(-)5 M), and (5) with allergen plus the peptido-leukotriene receptor antagonist iralukast (10(-)7 M to 10(-)5 M). Rings were first contracted with 10(-)6 M carbachol and then relaxed with salbutamol (10(-)9 M to 10(-)4 M). The concentration-relaxation curve to salbutamol was shifted significantly to the right in the rings challenged with allergen only compared with control rings. In the rings challenged with allergen plus nedocromil sodium (10(-)6 M and 10(-)5 M) or iralukast (10(-)6 M and 10(-)5 M) the concentration-relaxation curves to salbutamol were significantly shifted to the left compared with rings challenged in saline alone, suggesting a protective effect against beta2-adrenoceptor dysfunction. Neither allergen plus cetirizine nor allergen plus indomethacin shifted significantly the concentration-relaxation curves to salbutamol compared with rings challenged in saline alone. We conclude that the release of peptido-leukotrienes may play a significant role in causing the allergen-induced beta2-receptor dysfunction in passively sensitized human bronchi.

Aged↗
PubMed1997

Allergen challenge of passively sensitized human bronchi alters M2 and beta2 receptor function.

We investigated whether antigen challenge may alter M2 and beta2 receptor function in isolated passively sensitized human bronchi. Bronchial rings (2-4 mm internal diameter) were obtained from 12 patients. Passive sensitization was induced by serum containing high IgE levels to Dermatophagoides pteronyssinus and Dermatophagoides farinae. Rings from six patients were used to study M2 receptor function by incubating with cumulatively increasing concentrations (10(-8) M to 10(-4) M) of pilocarpine and applying electric field stimulation (EFS) at 24 Hz. The rings from the other six patients were used to study beta2 receptor function by precontracting with carbachol 10(-6) M and adding cumulatively salbutamol (10(-9) M to 10(-4) M). Additional rings from these patients were used to determine whether dysfunction occurred distal to cAMP production by precontracting with carbachol 10(-6) M and adding cumulatively theophylline (10(-9) M to 10(-4) M). The attenuation of EFS-induced force by pilocarpine and the relaxation of carbachol-precontracted rings by salbutamol were less in challenged than in control and sensitized rings. No difference between challenged, sensitized, and control rings was observed with theophylline. We conclude that allergen challenge in passively sensitized isolated human bronchial rings may result in M2 and beta2 receptor dysfunction without involving mechanisms distal to cAMP formation. It appears that products from inflammatory cells recruited from blood are not necessary for this receptor dysfunction.

Adrenergic beta-Agonists↗
PubMed1992

Airway inflammation and occurrence of delayed bronchoconstriction in exercise-induced asthma.

We studied nine asthmatic patients with a history of exercise-induced asthma (EIA) in order to investigate whether inflammatory changes in the airways occur after exercise and are eventually associated with the development of a late-phase asthmatic response. On two separate study days, bronchoalveolar lavage (BAL), bronchial lavage (BL), and bronchial biopsy (BB) were performed 3 h after an exercise or a methacholine (MCh) challenge. On two other separate occasions, FEV1 was monitored for 12 h after identical exercise and MCh challenges not followed by BAL, BL, and BB. We found a greater percentage of eosinophils in BAL after exercise versus MCh challenge (p < 0.05). In five patients, BAL eosinophils after exercise were > or = 2% of total inflammatory and immunoeffector cells. In three of these patients an FEV1 fall > 20% of control was recorded 5 to 12 h after exercise. However, two of these patients had 2% or more eosinophils in BAL and similar late falls of FEV1 after MCh challenge. The percentage of degranulating mast cells in BB was higher (p < 0.05) after EIA than after MCh, but no significant differences were found in BL histamine and leukotrienes. We conclude that (1) exercise may enhance mast cell degranulation and eosinophilic inflammation of the airways, and (2) a delayed bronchoconstriction after exercise is not specific to EIA but is more likely the result of fluctuations in lung function associated with airway inflammation.

Adult↗
PubMed1991

Increased numbers of mast cells in bronchial mucosa after the late-phase asthmatic response to allergen.

We examined the characteristics of allergen-induced inflammation of the bronchial mucosa in asthmatic patients. Studies were carried out 4 h (eight patients) and 24 h (nine patients) after allergen inhalation challenge; 10 patients were not challenged and served as control subjects. We found that in the control group the ratio of degranulating to granulated mast cells was higher in patients with than in patients without late-phase response. In patients studied 4 h after allergen challenge the total number of mast cells was not significantly different from that in control subjects; the ratio of degranulating to granulated mast cells was increased similarly in patients with and without late-phase response. Among patients studied 24 h after allergen challenge, those who had developed the late-phase response had an increased (p less than 0.05) number of mast cells as compared with patients who had not developed the late-phase response, the number of mast cells was significantly correlated with the severity of the late-phase response (r = 0.80; p less than 0.001). The numbers of eosinophils and mononuclear cells and the morphologic abnormalities of bronchial structure (altered ratio of cylindrical to goblet cells, thickening of the basement membrane, and edema and angiectasis of lamina propria) were similar in the different groups of patients. We conclude that the inflammatory events leading to the development of the late-phase asthmatic response to allergen represent a stimulus for an increase in the number of mast cells in the bronchial mucosa.

Adult↗
PubMed1984

A sequential protocol for the optimization of diagnostic procedures in hepatology.

The aim of this paper is to present a sequential protocol to be used in clinical practice for the detection of liver diseases, based on clinical history, physical examination, and laboratory investigation. The evaluation of the protocol efficacy was carried out on a sample of 288 subjects (92 normal, and 196 affected by various liver alterations) by comparing the obtained results with reference classifications independently performed on the basis of all available subject records (including many more laboratory tests than the ones used in the protocol). A cost-benefit analysis was also carried out, based on the resident population of Regione Piemonte, comparing the protocol with two other simpler ones. Results show that the proposed protocol allows a considerable reduction of costs, showing a high estimated efficacy for clinical use.

Adolescent↗
PubMed1984

Advanced modeling and identification techniques for metabolic processes.

This paper will be devoted to demonstrating that a better understanding of complex metabolic processes requires a deep and reliable interpretation of much experimental data. Indeed this aim cannot be satisfied without the use of advanced modeling and identification techniques and their deep critical analysis. In fact, complete procedures should consider all the following steps: (1) definition of scopes, (2) prior information and hypotheses, (3) choice of experimental conditions, (4) derivation of possible classes of models, (5) parameter estimation, (6) errors evaluation, (7) validation and ordering of the identified models. This paper will mainly consider steps 4, 6, and 7 which are certainly the less assessed ones. However some real advances have been obtained in recent years which deserve to be more widely known and applied in practical problems. This paper will review such important contributions and will show, by means of applied examples, how they can be useful in avoiding ambiguities and incorrect interpretation of data and in evaluating the credibility of the inferred results.

Animals↗
PubMed1983

Qualitative and quantitative evaluation of liver diseases: functional classifications.

The problem of the best use of experimental data for qualitative and quantitative evaluation of liver disfunction is analysed. Only statistical procedures for classification are considered. Emphasis is placed on a complete description of the most important steps that must be performed (degree of clustering of the data, validity of the hypotheses underlying the statistical methods used, meaning and adequate use of the reference classification, reliability of the different statistical methods used, information content of the laboratory tests studied) since the omission of any of them may contribute to a misleading interpretation of the overall results or may prevent significant practical utilization. An application to BSP tests is carried out: results obtained from 350 subjects are presented and discussed. A classification related to the main functional aspects of liver impairment was chosen. Different combinations of the parameters obtained from BSP blood disappearance curve--initial disappearance rate (K1), 45 min-retention of total (RT45) and conjugated (RC45) BSP- and different mathematical algorithms are compared. Five classes (N, normal subjects; PN, paranormal subjects; H, prevalent hepatocellular damage; C, prevalent cholestatic damage; HC, heavy combined damages) can be satisfactorily discriminated with all three parameters (K1 + RT45 + RC45); however K1 + RC45 give almost the same results and represent an interesting compromise between data information content and laboratory complexity.

Diagnosis, Computer-Assisted↗
PubMed1983

Description and simulation of a physiological pharmacokinetic model for the metabolism and enterohepatic circulation of bile acids in man. Cholic acid in healthy man.

A multicompartmental pharmacokinetic model based on physiological principles, experimental data, and the standard mathematical principles of compartmental analysis has been constructed that fully describes the metabolism and enterohepatic cycling in man of cholic acid, a major bile acid. The model features compartments and linear transfer coefficients. The compartments are aggregated into nine spaces based on physiological considerations (liver, gallbladder, bile ducts, jejunum, ileum, colon, portal blood sinusoidal blood, and general circulation). The transfer coefficients are also categorized according to function: flow, i.e., emptying of gallbladder or intestinal spaces, and circulation of the blood; biotransformation, i.e., conjugation, deconjugation, or dehydroxylation; and transport, i.e., active or passive transport. The model is made time dependent by introducing meals, which trigger discrete increases in gallbladder emptying and intestinal flow. Each space contains three compartments. For cholic acid, these are unconjugated cholic acid, cholylglycine, and cholyltaurine. The model was then used with all existing experimental data to simulate cholic acid metabolism in healthy man over a 24-h period. Satisfactory agreement was obtained between simulated and experimental results for serum bile acid levels, hepatic bile acid secretion, and bile acid secretion into the intestine. The model was also used to classify 16 clinical instances in which the enterohepatic circulation of bile acids is altered by drugs or disease. The model can be extended to describe completely the metabolism and enterohepatic circulation of any bile acids in man in health and digestive disease. The model should also be broadly applicable to the description of the pharmacokinetics of all other drugs whose metabolism is similar to that of bile acids, i.e., drugs for which there are tissue and bacterial biotransformations, enterohepatic cycling, and appreciable first-pass clearance.

Bile Acids and Salts↗
PubMed1978

Discrimination of hepatobiliary diseases by the evaluation of bromsulfophthalein blood kinetics.

Blood BSP kinetics was studied by compartmental analysis in 10 normal subjects, 11 cirrhotic patients, and nine patients suffering from obstructive jaundice. Plasma levels of both free and conjugated BSP were determined at different times after intravenous injection of a standard dose (5 mg/kg body weight) of the dye. A six-compartment model was found suitable for the correct evaluation of hepatobiliary function, but simpler models cannot be used in this respect. Some of the parameters of the model can be adequately evaluated in the studied measurement situation and are used to carry out a diagnostic discrimination; they are lambda21 (transfer constant from blood to liver cells), alpha1 (expression of both conjugating and excretory activity), and beta (related to the blood level of conjugated BSP). It is shown that the values of these parameters allow a fairly good separation among the three groups of subjects under study.

Adult↗
PubMed1975

Structural analysis of compartmental models for the hepatic kinetics of drugs.

The structure of some compartmental models for the analysis of the hepatobiliary kinetics of bromosulphalein (BSP) was studied in order to evaluate their adequacy in the estimation of the processes involved in the hepatic metabolism of drugs, namely uptake, conugation, and biliary excretion. Biological measurements were obtained from 4 cholecystectomized patients with a biliary T-tube. Blood and bile specimens were taken at various intervals after the administration of a single intravenous dose of BSP and analyzed for both direct BSP quantitation and chromatographic separation and estimation of BSP metabolic fractions. The structural analysis was carried out by using a mathematical model that described the kinetics of BSP. By means of computer simulations different measurement situations were analyzed, showing for each experimental condition the available information and the degree of accuracy of each estimated parameter. The obtained results show that the use of compartmental models can provide a useful theoretical framework by which the experimental data can be interpreted for the evaluation of the hepatobiliary metabolism and for a discriminant analysis between different physiopathological conditions.

Bile↗