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P Colombo

Publications and source records attributed to P Colombo.

At least 73 records · Page 4Linked 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

Microparticles of novel branched copolymers of lactic acid and amino acids: preparation and characterization.

The preparation and characterization of microparticles produced from a new class of functionalized, biodegradable, comblike graft copolymers is presented. The copolymers are polyester-polyamino acid hybrids, composed of a poly(L-lactic acid-co-L-lysine) (PLAL) backbone, and poly(L-lysine), poly(D,L-alanine) or poly(L-aspartic acid) side chains extending from the lysine residues of PLAL. The microparticles have been characterized with regard to their surface properties, morphology, and size. Thus, electron spectroscopy for chemical analysis data and results of Zeta potential measurements suggest that the polyamino acid side chains tend to concentrate at the surface of the particles. Also, analyses by environmental scanning electron microscopy and confocal scanning laser microscopy indicate that particles carrying poly(lysine) chains have an unusual porous structure, most probably due to the combined effects of the amphiphilic, polyelectrolyte, and chemical nature of the composing copolymer, as well as of the particular preparation technique employed. The capabilities of the microparticles to serve as carriers in controlled drug release and delivery devices were demonstrated by encapsulation and release of rhodamine B, a low molecular weight drug model.

Aerosols↗
PubMed1999

Ionized prodrugs of dehydroepiandrosterone for transdermal iontophoretic delivery.

PURPOSE: The aim of this work was to synthesize ionized dehydroepiandrosterone (DHEA) prodrugs with higher water solubility, useful for iontophoretic transdermal application. METHODS: The synthesized derivatives were characterized and tested for sensitivity to chemical and enzymatic hydrolysis. Solid state and solution stability was also determined. Transdermal iontophoretic anodal transport in vitro was studied using excised rabbit skin. RESULTS: Two DHEA ionized prodrugs were synthesized: PRO1, a primary amine derivative, and PRO2, a quaternary ammonium salt. The two derivatives possess higher water solubility and lower octanol/saline partition coefficients than DHEA. Prodrugs were sensitive to enzymatic hydrolysis; in particular the primary amine was hydrolyzed faster than the quaternary salt by esterase from porcine liver in vitro. Transdermal flux of the two prodrugs was slightly higher than the parent drug. In the case of passive diffusion, only DHEA was found in the receptor compartment, indicating the complete breakdown of the prodrug in the skin. Current application gave higher drug flux and a significant amount of prodrug was found in the receptor. CONCLUSIONS: The use of ionized prodrugs of DHEA can increase the flux attainable during transdermal anodal iontophoresis by up to 7 times, but they are useful for passive transport as well.

Administration, Cutaneous↗
PubMed1999

Role of oesophageal manometry in clinical practice.

The present study evaluates the role of oesophageal manometry in clinical practice. Over 5 years, 347 consecutive patients were evaluated in our oesophageal laboratory. The reasons for referral were: dysphagia (11.5%), gastro-oesophageal reflux disease (GORD) (46.7%), non-cardiac chest pain (28.5%), connective tissue disease (6.9%) and other symptomatology (6.3%). Patients were classified into the following five groups according to the referral diagnosis: dysphagia (40 patients), gastro-oesophageal reflux disease (GORD) (162 patients), non-cardiac chest pain (99 patients), connective tissue disease (24 patients) and other symptomatology (22 patients). Abnormalities in oesophageal motility were detected in 90% of patients with dysphagia, in 40.1% of patients with GORD, in 47.5% of subjects with non-cardiac chest pain, in 45.8% of patients with connective tissue disease and in 18.2% of subjects with other symptomatology. The high prevalence of abnormalities in the dysphagia group was statistically significant (p < 0.001), and the range of 95% confidence intervals (0.81-0.99) suggests that the value found may be a reasonably good estimate of percentage of anomalies detectable in the dysphagia patient population. In the dysphagia group, the initial diagnosis was confirmed in 40% of patients and changed in 52.5%; in only 7.5% of cases were the manometry results not relevant for determining an appropriate diagnosis. Manometry substantially contributed to patients receiving the correct treatment in 82.5% of cases (p < 0.001 among all groups). In the GORD group and in the non-cardiac chest pain group, the results of manometry were not relevant for confirming or changing a diagnosis in 59.8% and 53.5% of cases respectively; nevertheless, in both groups, on the basis of manometry results, the treatment was changed in 42.5% of patients (p < 0.01 vs. other symptomatology group). In conclusion, on the basis of the present data, we can emphasize the usefulness of oesophageal manometry assessment in patients with dysphagia or non-cardiac chest pain, with negative routine examinations, and also in patients with refractory GORD who have been considered for antireflux surgery.

Aged↗
PubMed1999

[Blunt traumatic rupture of the diaphragm].

Lesions of the diaphragm are uncommon but important complications of blunt thoraco-abdominal traumas. Their incidence is increasing over the last decades as a consequence of the increase of the road traumatology. Preoperative diagnosis is often difficult especially when the diaphragmatic lesion is associated with other skeletal or visceral injuries that may mask the clinical or radiological signs. The Authors report 12 cases of traumatic lesions of the diaphragm due to blunt trauma observed from 1980 to 1997 and that underwent surgery. In particular they discuss about the importance of an early diagnosis and a correct surgical approach to reduce morbidity and mortality. Nine patients were operated by laparotomy; thoracotomy was performed in one case and the combined approach in the last two patients.

Adult↗
PubMed1999

[Definition criteria for a magnetic resonance quality assurance program: multicenter study].

PURPOSE: We report the preliminary results of a multicenter trial aimed at defining methods, reference values and frequency of measurements for an MR quality assurance program. In particular, we stress the definition of two attention levels (investigation and intervention) for image uniformity and signal-to-noise ratio (SNR) by means of short- and long-term measurements. MATERIAL AND METHODS: The short-term protocol consisted of 10 successive spin-echo (SE, 2 echoes) acquisitions and was repeated after 24 hours. Measurements were made with the same test phantom which was circulated among all the participating centers. Image uniformity and SNR were evaluated using the software available on each MR unit. The long-term protocol, consisting of a single SE acquisition with the same parameters used for the short-term one, was performed once a month for 12 months. A mid term protocol was also performed twice a week for 5 weeks, and the analysis of the results is still in progress. RESULTS AND DISCUSSION: The short-term protocol results allowed absolute comparison of system performance. Uniformity and SNR were significantly different among centers (p < 0.05), also in the statistical comparison of two MR units of the same model (Siemens Magnetom SP63-1.5 T). Overall, three 1.5 T systems provided similar SNR values, while the results obtained for the 1 T system were markedly lower (51% of the maximum). This result can be explained by the dependence of the analytical expression of SNR on the magnetic field. The other 1.5 T system performed more poorly than the others operating at the same magnetic field. This difference can be explained by the specific characteristics of the coil and by technological aging. Because of the small sample size (5 units), the maximum variation coefficients (3% for the first echo and 3.5% for the second one) were assumed as a reference value for the both parameters (SNR and uniformity). These values were used for the long-term analysis: at every measurement the evaluated parameter was statistically compared with the result of the previous month. We propose to set an investigation level at p = 0.05: when the newly measured parameter differs from the previous value (p < 0.05), we should investigate if this is due to a normal long-term variation or to a system fault. The intervention level is then defined as the 95% prediction interval of the evaluated parameter regression vs time. Measurements that do not fall within the prediction interval are not used for future statistics. CONCLUSIONS: Some preliminary results concerning SNR and uniformity were obtained in the investigation performed on 5 MR systems to define methods and references for a Quality Assurance program. We introduced an "investigation level" and an "intervention level" related to short-term and long-term variability. The investigation levels could be a useful reference value to predict the short-term variability of an MR system with similar characteristics, thus avoiding a long and onerous series of measurements. Concerning the optimization of measurement frequencies, the preliminary analysis of these results showed that a daily measurement frequency is excessive in stable equipment conditions, while monthly measurements showed that the investigation level was often exceeded. However, frequency optimization will be investigated after the analysis of the mid-term measurements, which is still in progress.

Magnetic Resonance Imaging↗
PubMed1999

[Cecum-colon invagination due to cecal adenocarcinoma. Apropos of two cases].

The Authors report in an elderly patient a ceco-colic intussusception caused by carcinoma of the cecum, and evaluate etiology and pathogenesis, the most frequently affected anatomical sites, and the various clinical manifestations of the disease. Regarding the latter, the Authors emphasize chronicity of the suboccf1p4ve status in the adult patient vs. the clinical picture of intussusception in the paediatric one. Hemicolectomy represents the most common therapeutic approach, especially when intussusception is irreducible or with the evidence of severe colonic ischemia.

Adenocarcinoma↗
PubMed1998

Identification of an immunodominant IgE epitope of the Parietaria judaica major allergen.

Par j 1.0101 is one of the two major allergens of the Parietaria judaica (Pj) pollen, and its three-dimensional structure was built by three-dimensional structural homology modeling. The resultant model was used to identify putative IgE binding regions. Western blot analysis of gene fragmentation products showed that the 1 to 30 region was capable of binding specific IgE from a pool of sera (n = 30) of patients allergic to Pj pollen. Using the structural model as a guide, deletion and site-directed mutagenesis of the 1 to 30 region was performed, and the amino acids involved in IgE binding were identified. In addition, a synthetic peptide covering the 1 to 30 region was capable of binding human IgE without triggering histamine release from basophils of Pj allergic patients (n = 6) and thus represents a haptenic molecule with potential use as an immunotolerant agent. This epitope is also present on the Par j 2.0101 major allergen representing a common IgE epitope. It is an immunodominant epitope, since it was capable of inhibiting 30% of all specific IgE against the Pj major allergens, and therefore, it might be a candidate for the future development of immunotherapeutics.

Allergens↗
PubMed1998

In vitro acyclovir distribution in human skin layers after transdermal iontophoresis.

The purpose of the present work was to study the in vitro distribution of acyclovir in human skin layers after iontophoresis, applied in order to increase the amount of drug in the basal epidermis, site of Herpes simplex infections. Experiments were done with Franz diffusion cells applying, as donor, acyclovir solutions (pH values: 3.0 and 7.4) or a commercial cream. Quantification of drug at different skin depths was performed by horizontal slicing of frozen skin, and drug extraction and analysis by high-performance liquid chromatography. Seven h of transdermal iontophoresis (0.5 mA cm-2 induced an accumulation of acyclovir in epidermis and dermis ranging from 80 to 150 micrograms cm-3, characterized by homogeneous distribution of the drug in skin layers. After short current application time (30 min) however, the concentration profile of drug in skin was not significantly different from the obtained after seven h of passive diffusion, employing pH 3.0 donor solution. After 30 min of iontophoresis, the acyclovir reservoir on the skin was maintained for up to five h producing a dramatic increase of drug concentration in skin, evening out over 80 micrograms cm-3 until a depth of 300 micrograms. Acyclovir can be accumulated at target site more quickly and maintained at higher level through application of a iontophoretic pulse and by keeping the drug reservoir on skin.

Acyclovir↗
PubMed1998

Integrin laminin receptor profile of pulmonary squamous cell and adenocarcinomas.

The differential expression of laminin receptors has been shown to modulate the invasive capability of malignant cells. We have investigated the reactivity of human pulmonary squamous carcinomas (SSC, n = 20) and adenocarcinomas (ADC, n = 20) with monoclonal antibodies to the cytoplasmic and extracellular domains of the integrin subunits alpha3 and alpha6. Integrins containing these subunits are laminin receptors. Monoclonal antibodies to beta1 and beta4 subunits, the beta1C splice variant of beta1, as well as to Ki-67, were also used. Reverse transcription polymerase chain reaction (PCR) single-strand conformational polymorphism analysis was done to detect possible mutations in the cytodomains. All carcinomas expressed alpha3 extensively; alpha3 expression predominated (40 of 40) over alpha6 (25 of 40). In all alpha6-positive carcinomas, alpha6A was expressed, whereas alpha6B was weakly expressed only in some of them. No mutations of the intracytoplasmic domain A of alpha3 and of the A or B intracytoplasmic domains of alpha6 were shown. Notably, in normal bronchial epithelium, alpha6 colocalized with beta4, whereas in the tumors, alpha6A frequently overlapped with beta1 in a circumferential pattern; alpha6beta1 coexpression was also shown by coprecipitation experiments. Strong and extensive beta4 reactions were invariably polarized at the cell/stroma interface in SCC and ADC. An inverse correlation was found between the expression of beta1C and Ki-67. The prevalence of alpha6A in pulmonary SCC and ADC is in contrast with previous results in colonic ADC in which alpha6B prevails, and alpha6 predominates over alpha3. The absence of mutations of the cytodomains suggests that the integrin subunits of these carcinomas are potentially active. Predominance of alpha3 over alpha6 and of alpha6A over alpha6B may contribute to explain the aggressive and metastatic behavior of lung carcinomas.

Adenocarcinoma↗
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

Changing strategies of lung biopsies in diffuse lung diseases: the impact of video-assisted thoracoscopy.

The aims of this report were: 1) to compare the strategy of bioptic approach in Italy during the last 4 yrs with a previous period; and 2) to compare efficacy and safety of video-assisted thorascopic lung biopsy (VTLB) versus OLB. We retrospectively evaluated: 1) the strategy of the bioptic approach in the Milan Sarcoid Clinic in the years 1992-1995 (201 patients) versus 1988-1991 (197 patients); and 2) data from 65 VTLB procedures in the years 1992-1995 versus 68 OLB procedures in the years 1988-1991 performed in patients with diffuse lung disease. It was found that the use of OLB (17-9%), mediastinoscopy (15-5%), and scalene node biopsy (20-7%) decreased, whereas transbronchial biopsy (TBB) increased (11-17%). VTLB biopsy is now performed in 17% of patients. VTLB compares favourably with OLB as there is less need for analgesia (7.5+/-7.5 versus 17.5+/-8.0 methadone mg i.m.: p<0.001), lower blood loss (61+/-58 versus 156+/-84 mL in the first postoperative day: p<0.001), and shorter postoperative stay (4.7+/-1.6 versus 5.7+/-1.4 days: p<0.001). Specimen adequacy (98.6 versus 985%) and diagnostic accuracy (86.1% VTLB, versus 92.6% OLB: p>0.05) were the same in the two groups. In conclusion, video-assisted thoracoscopic lung biopsy is replacing both mediastinoscopy and open lung biopsy. It is at present the best option when a surgical procedure is required for histological confirmation of diffuse lung disease.

Adult↗
PubMed1998

The late follow-up of chronic sarcoid patients previously treated with corticosteroids.

AIM OF THE STUDY: The aim of the study was to evaluate, in a white population with chronic sarcoidosis, the rate and pattern of relapses, the correlated factors, and the course of disease after prednisone withdrawal. METHODS: We have retrospectively examined the charts of 702 consecutive patients with histologically proven sarcoidosis, first seen in the Milan Sarcoidosis Clinic in the period October 1978-October 1994. 239 patients required corticosteroid therapy; in 82 it was possible to discontinue prednisone therapy and to have a follow-up of at least 18 months after withdrawal. RESULTS: A relapse, requiring a new course of steroids, was observed in 30 (36.6%) of the 82 patients (R group). The other 52 patients (No-R group) did not relapse during a mean follow-up of 36.8 +/- 24.8 months (range 18-125). There were no relapses after 3 asymptomatic years of prednisone withdrawal. Extrapulmonary sarcoidosis was a reason for giving therapy in 46.6% of patients in the R group, vs 23.0% in the No-R group (P < 0.05). The first course of therapy lasted 22 months [median time; i.q. 11.5 to 34.5] in R group vs 26 months [i.q. 18 to 41] in No-R group (P > 0.05). The mean daily prednisone dose was higher in the R group: 17 mg [median value; i.q. 8.9 to 23.2] vs 10.6 mg [i.q. 8.1 to 13.8] in the No-R group (p < 0.05). Logistic regression confirmed the prognostic significance of mean daily prednisone dose and of extrapulmonary sarcoidosis at presentation (P < 0.01). A mild sarcoid activity at the time of withdrawal was still present in 51.9% of patients who did not relapse, and in 66.7% of patients who relapsed (p > 0.05). Relapse in the first year after withdrawal of prednisone therapy occurred in twenty-five of the 30 patients. The pattern of relapse was different from the initial manifestation in 5. Nine of the 30 patients could ultimately be weaned successfully from prednisone. CONCLUSION: Relapses occurred in 36.6% of cases, and their pattern was the same as the initial manifestation in the majority of cases. A mild sarcoid activity at the time of withdrawal is not a reason for continuing steroids when the disease is abating. In our white population severe irreversible pulmonary impairment is rare, and even patients requiring chronic therapy need low prednisone dosage, usually around 10 mg daily, to control the disease in the late course.

Adult↗
PubMed1998

[DRG/ROD: limits to their application in nephrology].

The ministerial decrees of 15/4/94 and 14/12/94 defined the new payment schedules for hospital services during ordinary and day hospitalization; the hospital discharge form (SDO) is the main source of this information. The services are defined by the classification of ROD ("raggruppamenti omogenei di diagnosi"), adapted from the American DRG ("Diagnosis related groups"), which have substituted the traditional system of payment by production factor. On the basis of the DRG identified and the length of hospital stay, the Region pays the hospital the cost of hospitalization. The main diagnosis at discharge, secondary diagnosis, complications and diagnostic/therapeutic procedures all contribute to the determination of 489 DRG. Groups of pathologies are reclassified into 25 MDC ("Major Diagnostic Categories"). The 11th MDC includes the uronephrological DRG (302-333). The nephrological sector has been penalized by the inadequate value given to related procedures and diagnostic limitations. In order to guarantee efficacious diagnostic and therapeutic procedures, without impoverishing the nephrological budget and reducing the management autonomy of the divisions and autonomous services with hospitalization, it is necessary to introduce quality controls and corrective measures to the procedures that maintain the value of diagnosis and comply with financial considerations.

Adolescent↗
PubMed1998

Control of hypertension in Italy: results of the "Study on Antihypertensive Treatment in General Practice (STAP)". Physicians Taking Part in STAP.

BACKGROUND: Various epidemiological surveys from different countries have documented the unsatisfactory control of arterial hypertension. The aim of this study was to assess the current status of treatment and control of hypertension in Italy. METHODS: A random sample of general practitioners (GP) working in several Aziende Sanitarie Locali (Local health offices-ASL) throughout Italy were invited to take part in the study. Each doctor had to recruit a random sample of 15-20 hypertensive patients receiving antihypertensive drugs among those attending his/her office for any reason. A standard medical history, specifically oriented to hypertension and its pharmacological treatment, was taken for each patient. Three blood pressure (BP) measurements were made, with the patient seated for at least 5 minutes, using an accurate automatic device (A&D UA-732), and the mean was taken as each patient's BP. RESULTS: A total of 73 GPs (17% of the invited sample), working in 14 Italian ASL (six in the north of the country, four in the center and four in the south and islands), agreed to participate in the study. They recruited an average of 17 patients each, for a total of 1204 hypertensive subjects (663 women and 541 men) 633 of whom were 65 years old or more, mean age 64 +/- 11 years, range 25-94 years. More than half (56%) had been taking antihypertensive drugs for at least five years; 42% were taking one drug, 40% two, 16% three and 2% four drugs. Respectively, 63% and 23% had systolic BP (SBP) > or = 140 and > or = 160 mmHg; 28% and 14% had diastolic BP (DBP) > or = 90 and 95 mmHg. In 71%, BP was < 160/95 mmHg, but only 33% had BP lower than 140/90 mmHg. BP control was similar in males and females, but worse in the elderly. Nine percent of patients complained of symptomatic side effects, usually mild. Only 8% admitted to poor compliance with the antihypertensive therapy, and their BP was significantly less well controlled. CONCLUSIONS: Control of BP in patients receiving antihypertensive drugs is still far from optimal in Italy, just as in other countries. This situation seems more related to the fact that doctors do not tackle the problem aggressively, than to the patients' degree of compliance with therapy.

Aged↗
PubMed1998

[Infections from extemporaneous catheters for hemodialysis. Experience in a center].

BACKGROUND AND AIMS: This study reports a retrospective evaluation of the predominance of infection in 67 dual lumen central venous catheters (CVC), 35 of which were positioned in the femoral vein by the nephrological team and 32 in the subclavian vein by anesthetists. METHODS: The microorganisms responsible for infection, the prevalence of clinically symptomatic infections, the relationship between CVC-correlated infection and the time the catheter remained inserted were evaluated, together with a comparison between the two different insertion sites. RESULTS: Culture tests, performed using Maki's semiquantitative technique, gave positive results in 16/67 (23.8%) cases. The main pathogenic agents found were Staphylococcus epidermidis (37.5%) and Staphylococcus aureus (31.2%). In 3/16 cases (18.78%) infections were clinically symptomatic. The mean permanence of CVC with positive cultures was not statistically different to the mean permanence of CVC with negative cultures (22.44 +/- 13.48 vs 18.38 +/- 17.76). The microorganisms isolated on femoral and subclavian catheters showed a comparable distribution and the prevalence of infection was not statistically different in the two insertion sites. CONCLUSIONS: In conclusion, in the absence of infection, the authors tend to keep working catheters in the site, thus avoiding repeated invasive manoeuvres for replacement and/or repositioning, whereas in the presence of suspected systemic infection they feel it is more prudent to remove the CVC without waiting for the results of the hemoculture, starting first empiric and then specific antibiotic treatment on the basis of the antibiogram.

Bacterial Infections↗