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Biomedical subjects

G Brambilla

Publications and source records attributed to G Brambilla.

At least 19 recordsLinked to original sources

Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

Journal Article↗

Advances in asthma and COPD management: delivering CFC-free inhaled therapy using Modulite technology.

Inhaled corticosteroids (ICS) and long-acting beta-agonists (LABA) are currently used in the management of asthma and chronic obstructive pulmonary disease (COPD). Localized targeted delivery of these drugs into the lungs is achieved by means of two types of inhalation devices; pressurized metered-dose inhalers (pMDIs) and dry powder-inhalers (DPIs). For environmental reasons, the chlorofluorocarbon (CFC) propellants used in pMDIs are now being replaced by ozone friendly hydrofluoroalkanes (HFAs). These new generation HFA-based pMDIs, developed to provide effective lung deposition of the active moiety, have a favorable safety and tolerability profile. However, HFA-based re-formulation of LABAs and ICS for pMDIs presents particular technical difficulties, especially in terms of ensuring dose content uniformity. This review focuses on the technology and clinical efficacy of the HFA solution pMDIs using Modulite platform technology (Chiesi Farmaceutici S.p.A). Modulite technology allows the development of HFA solution formulations that can mimic the established CFC-based drug formulations on a microgram to microgram basis and provides formulations with novel particle size distributions that improve on existing delivery systems; by manipulation of aerosol clouds and particle size, the delivery of HFA-formulated drugs can be optimized to either achieve fine particle fractions and deposition patterns similar to established CFC-based drug formulations, thus facilitating the transition to new environment-friendly pMDIs in the clinical setting, or achieve finer drug particles able to penetrate deeper into the bronchi for targeted drug delivery as medical need may dictate. Long-term, multiple-dose clinical studies of Modulite formulations of beclomethasone dipropionate (BDP), budesonide and formoterol have been demonstrated to be therapeutically equivalent to their respective previously established CFC or DPI formulations. As a result, a number of Modulite pMDIs have either recently gained regulatory approval in several European countries, or have completed clinical trials and are in the regulatory submission phase. Availability, in pMDI form, of drugs like formoterol, ICSs, and ICS/LABA combinations, all central to the effective management of asthma and COPD, is therefore expected to impact positively in assuring the continued availability of vital treatment options to patients and physicians.

Adrenal Cortex Hormones↗

Seasonal patterns of hospital treatment for inflammatory bowel disease in Italy.

AIM: It is still debated whether clinical flare-ups of chronic inflammatory bowel disease follow a seasonal pattern, and the various reports are based on general practitioners' records or hospital discharge charts. There are, however, no specific figures for treatment in hospital gastroenterology units, which serve as a reference point for these disorders. This study was therefore designed to investigate whether there is a seasonal pattern in admissions for inflammatory intestinal disease in Italy, differing from what is generally known about gastrointestinal pathologies, since there are no nation-wide figures on the subject. METHODS: The RING (Ricerca Informatizzata in Gastroenterologia) project is an observational study collecting hospital discharge forms from 22 centers in Italy. RESULTS: From winter 2000 to autumn 2003, the 22 gastroenterology units participating in the RING project discharged 32,357 patients following ordinary hospital admissions. Of these, 2,856 (8.8%) had a main diagnosis of inflammatory bowel disease: 1,541 Crohn's disease, and 1,315 ulcerative colitis. No seasonal patterns were detected for either category, or when the analysis was done by age, sex and site of disease. CONCLUSIONS: The most serious flare-ups of inflammatory bowel disease, i.e. those requiring routine hospital treatment, do not appear to follow any seasonal pattern, regardless of the site of the disease or the patient's age or sex.

Adult↗

Modulite: a simple solution to a difficult problem.

The development of HFA-based pMDIs has proved difficult due to differences in the physico-chemical properties of CFC and HFA propellants. However, the development of solution formulations instead of suspensions has provided a way to formulate products whose cloud characteristics can be modulated in a controlled manner by permitting different formulation and device hardware variables. The new approach has proved successful in formulating several different drugs including steroids and has now been applied to developing a formoterol Modulite solution formulation characterized by good chemical stability, delivery performance, and clinical results.

Aerosol Propellants↗

Idiopathic recurrent acute pericarditis: familial Mediterranean fever mutations and disease evolution in a large cohort of Caucasian patients.

Idiopathic recurrent acute pericarditis (IRAP) is suspected to be an autoimmune phenomenon. We studied 46 consecutive patients. We looked for: 1) the occurrence of new diagnoses of autoimmune diseases during our follow up; 2) HLA typing; and 3) the presence of the most frequent mutations linked to familial Mediterranean fever (FMF gene or MEFV). HLA typing was done in 21 patients at loci B, DRB1, DQA1 and DQB1. MEFV gene was looked in 23 patients using specific primers. During the follow-up we made a new diagnosis of primary Sjögren's syndrome in four patients (8.7%) and of rheumatoid arthritis in one patient (2.2%). HLA B14, DRB1*01 and DQB1*0202 were significantly more prevalent, but we did not find a typical HLA typing. MEFV gene was searched: exon 10 was checked by sequence and the E148Q mutation by restriction site analysis. No mutations were found. In conclusion, the prevalence of definite immunorheumatological diseases and the absence of the mutations linked to FMF reinforce the notion that idiopathic acute recurrent pericarditis is an autoimmune condition.

Arthritis, Rheumatoid↗

Identification and quantification method of spiramycin and tylosin in feedingstuffs with HPLC-UV/DAD at 1 ppm level.

The use of the two macrolides antibiotics Spiramycin (S) and Tylosin (T) as growth promoters in animal feeding has been recently withdrawn in the European Union due to a concern about the outbreaks of farmacoresistance fenomena as a possible hazard for humans. For feed additives monitoring purposes, an analytical method has been developed for their extraction, purification and identification in different animal feedingstuffs (pelleted beef, pig, poultry feeds and calves milk replacer) at a minimum performance required limit (MRPL) of 1 microg g(-1) (ppm). Such limit has been established according to the lowest dosage of additives still able to elicit an appreciable growth promoting effect. Blank feeds were spiked at two concentration levels, 1.0 and 2.5 ppm in six replicates. After methanolic extraction, samples were cleaned up on SPE CN columns and extracts analysed in HPLC-UV/DAD, using a gradient elution. Detection limits, calculated as the tree time mean noise of 20 blank feeds, were 176 and 118 ng g(-1) for S and T, respectively. Results show good repeatability (CV% not exceeding the value of 15) and mean recovery in the range of 99-74% and 81-53% for S and T, respectively, at 1 ppm. When the standards were injected up to 250 ng the chromatographic method can resolve the components of analytes (Spiramycin I, II and III; Tylosin A and B) but can not resolve the components on real feed samples at the spiked levels considered. For this reason the identification and quantification of analytes on matrix were carried out considering the main compound of the drugs (Spiramycin I and Tylosin A). As a verification, the overlapping of UV spectra in the range 220-350 nm between analytical standards and the compounds in the matrix were considered.

Animal Feed↗

Traumatic acute subdural haematomas of the posterior fossa: clinicoradiological analysis of 24 patients.

BACKGROUND: We report 24 patients with a traumatic acute subdural haematoma of the posterior fossa managed between 1997 and 1999 at 8 Italian neurosurgical centres. METHOD: Each centre provided data about patients' clinico-radiological findings, management, and outcomes, which were retrospectively reviewed. FINDINGS: A poor result occurred in 14 patients (58.3%). Ten patients (41.7%) had favourable results. Patients were divided into two groups according to their admission Glasgow Coma Scale (GCS) scores. In Group 1 (12/24 cases; GCS score, > or =8), the outcome was favourable in 75% of cases. In Group 2 (12/12 cases; GCS score, <8), the outcome was poor in 91.6% of cases. Nineteen patients underwent posterior fossa surgery. Factors correlating to outcome were GCS score, status of the basal cisterns and the fourth ventricle, and the presence of supratentorial hydrocephalus. Multivariate analysis showed significant independent prognostic effect only for GCS score (P<0.05). INTERPRETATION: acute posterior fossa subdural haematomas can be divided into two distinct groups: those patients admitted in a comatose state and those with a moderate/mild head injury on admission. Comatose patients present usually with signs of posterior fossa mass effect and have a high percentage of bad outcomes. On the contrary, patients admitted with a GCS of 8 or higher are expected to recover. In these patients the thickness of the haematoma (<1 cm) seems to be a guide to indicate surgical evacuation of the haematoma.

Adolescent↗

Extraction, clean-up and gas chromatography-mass spectrometry characterization of zilpaterol as feed additive in fattening cattle.

Zilpaterol is an adrenergic drug currently licensed in Mexico and South Africa as a feed additive for cattle close to consignment. In this study an analytical method to detect zilpaterol in commercial feeds was set up. The influence of extraction solvent and matrix was evaluated. The drug as a trimethylsilyl derivative was characterized by GC-MS, on a quadrupole detector, in the electron impact mode. Acidic extraction, solid-phase extraction C(18) non-endcapped clean-up and mass characterization on ions m/z 308, 291, 405, 390 provided zilpaterol recoveries >75.3% and repeatability <3.3% in feeds spiked in the range 30.0-120.0 ng/g. The limits of detection and quantification were 7.5 and 25.0 ng/g, respectively. Such limits are well below the dose of 5.0-20.0 microgram/g proposed as effective.

Animal Feed↗

Traceability of inbred and crossbred Cinta Senese pigs by evaluating the oxidative stress.

Previous studies on the oxidative stress in swine indicated a strong link between the values of reactive oxygen metabolites (ROMs), the subsequent antioxidant adaptive response (OXY) and the genetic selection. Such findings, mainly related to a cardiovascular inadequacy in lean, large muscle blocks and fast growing breeds, is associated with specific metabolic diseases such as porcine stress syndrome and mulberry heart disease. In this study, we investigated the oxidative stress parameters to trace the genetics of Cinta Senese (CS) pigs, a historical breed free-range reared in Siena countryside. Sera from CS (n = 24) and Large White x CS (LW x CS) (n = 24) groups around 120 kg body weight fed the same diet were sampled at slaughter. Sera from wild boars (WB) (n = 24) hunted in the same district were also considered. ROMs and OXY were evaluated in the three groups of swine. Significant differences by one-way anova (P < 0.05) between groups were found for both procedures. ROM levels were lower in WB (9.79 +/- 5.76 mm H2O2) and CS (18.02 +/- 7.42 mm H2O2), and highest in LW x CS (42.78 +/- 8.61 mm H2O2). OXY values ranged from 271.37 +/- 50.90 microm neutralized HOCl (WB) to 343.21 +/- 57.45 microm neutralized HOCl (LW x CS). Results indicated that the evaluation of the oxidative stress can effectively trace the CS pigs, thus aiding in preserving the overall specific traits of such a historical animal.

Animals↗

An overview of tests for animal tissues in feeds applied in response to public health concerns regarding bovine spongiform encephalopathy.

Enforcing the ban on meat-and-bone meal in feed for farmed animals, and especially ruminants, is considered an important measure to prevent the spread of bovine spongiform encephalopathy. The authors describe current analytical methods for the detection and identification of animal tissues in feed. In addition, recently approved requirements, such as the ban of intra-species recycling (practice of feeding an animal species with proteins derived from the bodies, or parts of bodies, of the same species) are described. In principle, four different approaches are currently applied, i.e. microscopic analysis, polymerase chain reaction, immunoassay analysis and near infrared spectroscopy or microscopy. The principal performance characteristics of these methods are presented and compared, and their specific advantages and disadvantages described. Special emphasis is also placed on the impact of rendering conditions, particularly high temperatures and on the use of molecular biology techniques.

Animal Feed↗

Determination of hexafluoroisopropanol, a sevoflurane urinary metabolite, by 9-fluorenylmethyl chloroformate derivatization.

A reversed-phase HPLC method with fluorescence detection for the quantification of hexafluoroisopropanol (HFIP) in urine is presented. HFIP, a metabolite of the inhalation anesthetic sevoflurane, is excreted mainly in urine as glucuronic acid conjugate. After enzymatic hydrolysis of the glucuronate, primary amino groups of interferent urinary compounds are blocked by reaction with o-phthalic dicarboxaldehyde and 3-mercaptopropionic acid, followed by labeling of HFIP with 9-fluorenylmethyl chloroformate. The derivatization reaction proceeds in a water-acetonitrile (1:1) solution at room temperature with a borate buffer of pH 12.5 as a catalyst. A stable fluorescent derivative of HFIP is formed within 5 min. The HFIP-FMOC derivative is separated by reversed-phase chromatography with isocratic elution on an octadecyl silyl column (33x4.6 mm, 3 microm) and guard column (20x4.0 mm, 40 microm), at 35 degrees C, and detected by fluorescence detection at an excitation wavelength of 265 nm and an emission wavelength of 311 nm. The method detection limit is 40 pg, per 10-microl injection volume, corresponding to 16 microg/l of HFIP in urine. The among-series relative standard deviation is <6% at 200 microg/l (n=6). As a preliminary application, the method was used to detect HFIP concentration in the urine of two volunteers exposed for 3 h to an airborne concentration of sevoflurane in the order of 2 ppm.

Calibration↗

Modulite: a means of designing the aerosols generated by pressurized metered dose inhalers.

Although popular, the pressurized metered dose inhaler generates coarse, fast moving clouds so that the fraction reaching the lung is small. These shortcomings can be redressed by Modulite which permutes the following variables: the non-volatile components of a solution formula, the actuator orifice geometry, the volume of the metered solution and the vapour pressure of the propellants. This permits the design of aerosols with chosen particle size and plume speed. This facilitates co-ordination of dose generation with inspiration, reduces oropharyngeal deposition and provides a mechanism for targeting drug delivery to different parts of the lung. These principles are exemplified by designing an HFA-propelled beclometasone dipropionate product which closely matches existing products which use chlorofluorocarbons.

Aerosol Propellants↗

[CPAP in acute pulmonary edema. Our experience of the nurse role in the out of hospital life support].

The evolution of the nurse role in out of hospital life support yielded to the employment of tools typical of in-hospital setting, like helmet delivered CPAP. Some elements in the use of this tool have been analyzed: indications, contraindications, application modality and protocol, patient's record, practical aspects of the treatment and problems related to the material employed. Data concerning the application of this technique in 21 patients confirm the indication for its use in advanced nurse out of hospital life support.

Contraindications↗

Use of molecularly imprinted polymers in the solid-phase extraction of clenbuterol from animal feeds and biological matrices.

Clenbuterol molecularly imprinted polymers (MIPs) as chromatographic stationary phase for the solid-phase extraction (SPE) of the drug from biological samples have been prepared. Propylene columns filled with 500 mg of clenbuterol MIPs have been tested with respect to their loading capacity, memory effects, selectivity toward related drugs (mabuterol, clenproperol, clenisopenterol, ritodrine) and specificity toward interferences arising from heterogeneous matrices such as animal feeds, bovine urine and liver. Analytes were concentrated on Extrelut 20 columns and the residues resuspended in 70% acetonitrile. Application, washing and elution fractions were collected and analyzed by HPLC-diode array detection. Results indicate this MIP approach in SPE is extremely selective for clenbuterol, mabuterol, clenproperol and clenisopenterol (>95% found in the eluate), with a loading capacity of about 20 microg/100 mg of stationary phase. Ritodrine showed a recovery rate of 51%. The molecular recognition mechanism is so specific to allow clenbuterol detection and identification by conventional detectors at level of interest (ppb) also from complex matrices such as feeds, urine and liver.

Adrenergic beta-Agonists↗