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Biomedical subjects

R Bettini

Publications and source records attributed to R Bettini.

At least 37 records · Page 2Linked to original sources
PubMed1999

Drug volume fraction profile in the gel phase and drug release kinetics in hydroxypropylmethyl cellulose matrices containing a soluble drug.

In the present work, the drug volume fraction profiles of a colored and very soluble drug, buflomedil pyridoxal phosphate, in the gel layer of initially glassy hydroxypropylmethyl cellulose matrices were studied, using image analysis of pictures of the matrices during swelling and release. The goal was to correlate the drug release kinetics with the dynamic behavior of the drug gradient in the gel layer. An inert (nonswellable) matrix, manufactured by substituting hydroxypropylmethyl cellulose with an inert polymer and containing the same amount of buflomedil pyridoxal phosphate, was prepared as well. The drug color gradient in the partially extracted region and the flux of this matrix were compared to the swellable matrix. The drug gradient in the dissolved drug gel layer of swellable matrices was observed. It was demonstrated that drug release kinetics does not only depend on drug diffusion and matrix erosion, but also on drug dissolution in the gel and on polymer relaxation.

Diffusion↗
PubMed1999

Physical properties of parabens and their mixtures: solubility in water, thermal behavior, and crystal structures.

The peculiar solubility behavior of propylparaben (propyl ester of 4-hydroxybenzoic acid) in aqueous solution, when tested separately and together with methyl-, ethyl-, and butyl-parabens, has been investigated in detail. The results clearly indicate that the decrease in solubility (approximately 50% compared to the solubility value of propylparaben alone) is typical of those mixtures containing also ethylparaben, as demonstrated by solubility experiments on binary, ternary, and quaternary mixtures of the parabens. Phase diagrams of all the six binaries show that propylparaben and ethylparaben are the only pair that form almost ideal solid solutions near the melting temperatures. Moreover, phase-solubility analysis shows that propylparaben and ethylparaben, at room temperature, can also form solid solutions whose solubility is related to the composition of the solid phase at equilibrium. To achieve an independent confirmation of the possible solid solution formation that supports the above interpretation of the solubility behavior, the crystal structures of the four parabens have been examined and isostructurality has been found to exist only between ethylparaben and propylparaben. Powder X-ray diffraction has also been performed on ethylparaben, propylparaben, and their solid solutions obtained by recrystallization from water. The progressive shift of distinctive diffraction peaks with phase composition clearly indicates that propylparaben and ethylparaben form substitutional solid solutions. The small value (<1) of the disruption index provides thermodynamic support for substitutional solid solutions based on isostructural crystals.

Calorimetry, Differential Scanning↗
PubMed1998

Partial permselective coating adds an osmotic contribution to drug release from swellable matrixes.

A swellable matrix tablet is described which is partially coated with cellulose acetate (CA) to obtain a film having the shape of a cup, whose permeability to water and solutes was altered by mixing increasing amounts of poly(ethylene glycol) 400 (PEG). The drug-release mechanism from such systems was assessed by carrying out drug-release experiments both in water and saline solutions. Drug permeability through the polymeric cup and SEM analysis on the films were also performed. It was found that the systems exhibited drug-release kinetics very close to linearity. The mechanisms governing drug release were (i) drug diffusion through the uncoated gel layer, (ii) drug transport through the gel layer due to the osmotic pressure difference, and (iii) drug diffusion through the cup pores. The relative importance of each contribution depended on the amount of PEG in the film. The systems with a cup containing 1%, 13%, and 33% PEG w/w behaved in part as osmotic systems, whereas the system having a permeable cup behaved as a hybrid reservoir system. These modifications of the coating permeability introduce a further possibility of modulating drug-release kinetics and lead to a reduced dependence of swellable matrix tablet release on environmental conditions.

Cellulose↗
PubMed1998

Multiple myeloma index: verification of a new prognostic approach with evaluation of treatment response.

BACKGROUND AND OBJECTIVE: Currently adopted prognostic criteria for multiple myeloma (MM) still lack reliable predictive ability to select subsets of patients for different therapies, in particular for intensive treatment protocols. In this work we aimed to test the prognostic value of the MM Prognostic Index (MMPI), developed in 1996 by Grignani et al. from Pavia University as a clinical and investigational tool. DESIGN AND METHODS: Ninety-three MM patients were eligible for the study. All received initial induction therapy based on a standard 6-month melphalan + prednisone (M + P) protocol. Clinical and laboratory parameters, conventional staging and bone marrow infiltration percentage and cytopathology (BMIC) were assessed at diagnosis, while treatment response (TR) was evaluated using criteria after induction therapy. Cox's multivariate survival analysis was applied on prognostic data. RESULTS: In our patients independent prognostic value was confirmed for British Medical Research Council staging, BMIC and TR, the three factors considered in MMPI. Risk classes obtained via MMPI identify patients with different outcomes; moreover, the index discriminates significantly among Stage II patients. INTERPRETATION AND CONCLUSIONS: This new approach to MM prognosis is simple and reliable from the prognostic point of view; it refers not only to neoplastic mass, but also to intrinsic proliferative capacity of the malignant clone and to tumor-host interactions. We recommend its adoption in clinical practice and in the evaluation and design of therapeutic trials.

Adult↗
PubMed1997

Drug reservoir composition and transport of salmon calcitonin in transdermal iontophoresis.

PURPOSE: The aim of the work was to study iontophoretic transdermal administration of salmon calcitonin (sCt) in rabbits, with particular attention to drug reservoir composition. A dry sCt disc, to be dissolved on the application site, was used for preparing the reservoir for transdermal iontophoresis. As a reference drug reservoir, a pad wetted with drug solution was used. METHODS: Experiments were done in rabbits depositing 100 IU of salmon calcitonin on skin and applying anodal iontophoresis. Serum calcium concentration was measured during iontophoresis, passive diffusion and after i.v. administration. Parameters such as pH value and reservoir type were examined. RESULTS: Transdermal iontophoresis of sCt elicited a decrease in the serum calcium level, whereas, in the absence of electric current, no significant fall was measured. Using the reservoir prepared from drug solution, anodal iontophoresis at pH 4.2 was more effective than at pH 7.4, probably due to higher sCt net positive charge. Using the reservoir prepared from dry disc, similar kinetics and extent of drug effect were observed at both pH values. The reservoir prepared from solid drug deposit concentrated sCt next to the skin. CONCLUSIONS: Anodal iontophoresis for transdermal calcitonin administration shows therapeutical applicability. The type of reservoir is an important parameter affecting sCt transdermal iontophoresis.

Administration, Cutaneous↗
PubMed1996

Delivery of nasal powders of beta-cyclodextrin by insufflation.

PURPOSE: Delivery of nasal powders of granulated beta-cyclodextrin by insufflation was studied in order to find the relationship between powder properties and delivery behavior. METHODS: Three nasal powder formulations, prepared by granulating beta-cyclodextrin with different binders, were delivered from a powder insufflation device, in which the dose to be emitted was loaded in a gelatin capsule. The delivery sequence of powder was recorded and characterized using an image analysis program. RESULTS: Particle size was the main parameter affecting nasal powder delivery, both as to the amount of dose sprayed and the aspect of cloud produced. Between 50-150 mu m of particle size a substantial change in delivery behavior of powders was observed. Powder of around 100 mu m in size showed useful insufflation characteristics for nasal delivery. Bioavailability of nasal formulations of progesterone/beta-cyclodextrin powders was discussed in term of delivery behavior. CONCLUSIONS: The formulation approaches for improving nasal delivery of powders require the use of size optimized carriers. Insufflation of powders over 50 mu m can favour the particle deposition by impaction, whereas for powders below 50 mu m, deposition by sedimentation is moved. beta-cyclodextrin is a suitable carrier for achieving high systemic availability following nasal administration of powder formulations.

Administration, Intranasal↗
PubMed1995

Drug diffusion front movement is important in drug release control from swellable matrix tablets.

Swellable controlled release devices of buflomedil pyridoxalphosphate in hydroxypropyl methylcellulose were prepared, and their swelling and release behavior was investigated. The drug release as a function of time was investigated for various system parameters. Three distinct fronts were observed during the swelling and release processes, i.e., a swelling, a drug diffusion, and an erosion front. The drug diffusion front could be readily determined due to the drug's yellow color. The relative positions of the fronts and the drug release rate were studied as functions of the initial porosity and the molecular weight of the polymer carrier. It was shown that the drug diffusion front best describes the overall release behavior of the system. The fractional drug release was a strong function of the dissolved drug gel layer thickness, which separates the diffusion front from the erosion front. The effect of drug solubility was also investigated by altering the pH and the ionic strength of the dissolution medium. It was shown that as drug solubility increased, the undissolved drug gel layer thickness decreased, again showing the importance of the movement of the diffusion front in controlling the overall release.

Delayed-Action Preparations↗
PubMed1995

Improved late potential analysis in frequency domain.

This work presents a technique to improve the identification of late potentials (LP) in patients affected by greater arrhythmogenic right ventricular disease (GARVD). Several authors have documented the correlation between GARVD and LP by means of time domain analysis. Moreover, the high incidence of bundle branch block in patients affected by GARVD suggests LP analysis in the frequency domain be performed. The method of spectral mapping of the ECG with Fourier transform was adopted. This consists in dividing the ST segment into 25 subsegments and estimating their frequency components by means of the fast Fourier transform. Recently, it was documented that this technique suffers from poor reproducibility of results. Low reproducibility is the consequence of an improper localization of the analysed QRS segments. An algorithm to increase the QRS end point identification reproducibility is proposed. An optimal QRS filter was adopted as well as a technique based on the Hilbert transform. This technique allowed the reliability of the normality factor estimates to be improved. The computed normality factors on the XYZ leads and on the vector magnitude were used to classify patients and healthy subjects; 28 patients affected by greater arrhythmogenic right ventricular disease and 35 healthy subjects were analysed in the study. High sensitivity was obtained with respect to GARVD and clinical sustained ventricular tachycardia by means of a cluster analysis technique. By applying the technique proposed in this paper the identification of LP in GARVD was increased from 47% to 88%, when clinical sustained ventricular tachycardia was documented, whereas in patients affected by GARVD but not prone to sustained ventricular tachycardia LP identification increases from 18% to 64%.

Algorithms↗
PubMed1994

Study of prognosis in Waldenström's macroglobulinemia: a proposal for a simple binary classification with clinical and investigational utility.

Prognostic evaluation of Waldenström's macroglobulinemia (WM) is unreliable, few studies considered prognostic factors in WM and only one was derived from a multivariate analysis. One hundred forty-four retrospective, previously untreated patients with clinically overt WM were studied to learn whether overall survival was related to any of the various clinical features presented at diagnosis. Patients were homogeneously treated with intermittent doses of chlorambucil for as long as this showed an effect on the monoclonal component. The population was randomly subdivided into a 90-patient exploratory sample, on whom investigation would be conducted, and in a 54-patient test sample, on whom the results would be validated. In the exploratory sample univariate analysis identified the following parameters as the most important for prognosis: age (< or > or = 70 years), platelet count (< or > or = 120 x 10(9)/L), presence or absence of an abnormal number of red blood cells in the urine, hemoglobin concentration (< or > or = 9 g/dL), erythrocyte sedimentation rate (< or > or = 110 mm at first hour), presence or absence of cryoglobulinemia and of weight loss. Cox multivariate analysis showed that only hemoglobin, age, weight loss, and cryoglobulinemia independently affected survival. These four clinical variables were also shown to be able to discriminate survival significantly in the test sample. Moreover, it was possible to demonstrate (both in the exploratory and the test sample) that clear-cut, albeit dichotomic, survival discrimination can be reached with the presence at diagnosis of either no more than one, or any two or more, of these four prognosticators. These simple clinical criteria could be the basis of an initial binary, prognostic classification of WM, which could help in differentiating therapy according to the severity of the disease, and in properly designing future clinical trials.

Adult↗
PubMed1993

Laser nephelometric evaluation of albumin, IgG and alpha 2-macroglobulin: applications to the study of alterations of the blood-brain barrier.

Cerebrospinal fluid and serum levels of albumin, immunoglobulin G and alpha 2-macroglobulin were determined by laser nephelometer in various pathological conditions: Guillain-Barré syndrome amyotrophic lateral sclerosis, lumbar disc herniation. These proteins are different due to their molecular weight, spacial conformation, CSF and serum concentrations and their CSF/serum quotient reflects the status of the blood-brain barrier. In the subjects group comparisons, albumin quotient and IgG quotient show a significant differentiations. The linear regression of albumin quotient compared to alpha 2-macroglobulin quotient behaves differently in the individual groups. The protein CSF/serum quotients are helpful in distinguishing the causes of alterations in the blood-brain barrier.

Adolescent↗
PubMed1993

Methylxanthine drug therapy in chronic heart failure associated with hypoxaemia: double-blind placebo-controlled clinical trial of doxofylline versus theophylline and bamifylline.

The effects of the methylxanthine drugs doxofylline, theophylline and bamifylline were investigated on the basis of clinical and gasometric parameters in hypoxic patients with chronic heart failure. A parallel, double-blind, randomized study was conducted in 48 in-patients with NYHA II-IV chronic heart failure with normo- or hypercapnic hypoxaemia. They were divided into three groups and then submitted to a 4-day run-in with placebo. Either doxofylline 800 mg b.i.d., theophylline slow-release 400 mg b.i.d. or bamifylline 1200 mg b.i.d. were administered orally in each group of 16 patients for 10 days. Exercise capacity was estimated through NYHA class modification. Gasometric determinations, including arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and oxygen saturation (SaO2), were measured from arterial blood samples at the time of enrollment (T-4), at the onset of xanthine therapy (T0) and at the end of the trial (T9). After 10 days' treatment, the NYHA class was found to be diminished in 50% of the doxofylline group, 50% of the bamifylline group and 44% of the theophylline group. PaO2 showed a > 15% increase in 75% of the doxofylline group, 56% of the theophylline group and 43% of the bamifylline group (responders). In all three groups the responders presented a highly significant enhancement in PaO2 and SaO2 (p < 0.01 T0 vs T9). Doxofylline exhibited the highest percent increase in PaO2 and SaO2 with respect to T0. The effects on cardiac rhythm showed a progressive heart-rate reduction in the doxofylline group, whereas patients receiving theophylline presented an increase rate of beating. In conclusion, the use of methylxanthines in patients with chronic heart failure seems to be particularly effective especially when a significant ventilatory dysfunction is present. Doxofylline appears to be specially useful because of its ability not to interfere with cardiac rhythm.

Aged↗
PubMed1992

Life-threatening tachyarrhythmias in athletes.

The arrhythmias in competitive athletes may be classified as "benign," "paraphysiological" due to prolonged athletic training, or "pathological" due to hemodynamic effects on the athletic performance-risk-arrhythmogenic substratum. Pathological arrhythmias include life-threatening forms that are severe enough to produce symptoms (presyncope, syncope, cardiac arrest) during athletic activity. These forms are in particular rapid VT, VF, torsades de pointes, preexcited atrial fibrillation, sinus atrial and AV block. Our study population includes 766 competitive athletes, mean age 21.1 years (74 top international level), investigated with a cardioarrhythmological work-up for symptoms and for arrhythmias from 1974 to June 30, 1991. Three leading categories, represented by 16 aborted sudden death, 8 sudden death, and 7 induced VF (by EES or TAP) athletes, are described. All athletes with life-threatening arrhythmias, previously as asymptomatic or with minor symptoms had an arrhythmogenic substratum due to underlying silent cardiopathy or primary arrhythmic disorders. Athletic activity can be regarded as a trigger of electrical destabilization.

Adolescent↗
PubMed1992

[Epidemiology of pathological cerebral impairment].

Among the over-65 aged patients of our division (848 in all), during a period of little more than a year, we wanted to determine the prevalence of dementia in absolute and per cent terms, using two neuropsychological tests for the evaluation of mental functions, estimating the most frequent forms according to their nature, referring to sex, considering different age groups and trying to find a connection with the pathologies that caused hospitalization and with particular social-environmental conditions. We attended also to the present therapeutical proposals and to the difficult problem of nursing demented people. We estimated the presence of a pathological cerebral impairment in 4% of the over-65 aged population; the prevalence reaches 3.5% in the group between 65 and 74 years and 12% in the one from 75 up to 80 years and over. 50% of dementia is due to Alzheimer's disease, which is more frequent among women, 26.5% to multi-infarction dementia (MID), which strikes more men, and 20.6% to a mixed form, degenerative and vascular; finally other pathologies can be responsible for dementia in the remaining percentage. It is difficult to find a certain relation between dementia and associated diseases, except for MID, which is clearly connected with cerebrovascular and cardiovascular disorders, as well as to consider particular social-environmental conditions as predisposing factors for cognitive impairment. At present, there is no way to remove causes of primary dementia with any kind of therapy, which is therefore only symptomatic. Families bear most of the burden of caring for patients. Most of Alzheimer victims remain at home and subject caregivers to prolonged emotional and physical stress, making them the "hidden victims" of the disease. Clearly, there is a desperate need for day-care help and nursing home-care facilities to make the final institutionalization less frequent or at least to delay it as much as possible.

Age Factors↗
PubMed1991

[Supraventricular reentry tachycardia and athletic fitness].

Paroxysmal supraventricular reciprocating tachycardias (PSRT) which are due to a different type of reentry including the atrioventricular reentry circuit of Wolff-Parkinson-White (WPW) syndrome, may disturb the professional career of an athlete. Moreover even severe episodes of preexcited atrial fibrillation of WPW may occur. PSRT in athletes may present various clinical consequences: unimportant symptoms, or severe hemodynamic effects on the athletic performance particularly during sports activity at intrinsic high risk. The athletes are evaluated by clinical protocol which includes Holter monitoring ergometric test, echocardiography study, thyroid check and transesophageal electrophysiologic study at rest and during exercise. The arrhythmological study should be carefully performed in order to exclude an underlying heart disease, to study electrophysiological mechanisms and possible hemodynamic effect sports activity relate of the inducible and clinical tachyarrhythmias. Sometimes, these PSRT may disappear after interruption of athletic activity because of modifications of electrophysiological conditions related to the sports activity.

Electrocardiography, Ambulatory↗