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Biomedical subjects

P Colombo

Publications and source records attributed to P Colombo.

At least 37 records · Page 2Linked to original sources
PubMed2003

Effect of loperamide on gastro-oesophageal reflux.

BACKGROUND: We have recently shown that morphine reduces gastro-oesophageal reflux (GOR) by stimulating opioid receptors. Our aim was therefore to investigate the effect of loperamide, a peripheral opioid agonist, on GOR. METHODS: Nine patients with GOR disease underwent two ambulatory 24-h intra-oesophageal pH monitoring sessions separated by a period of at least 7 days under double-blind randomized conditions during the administration of placebo or loperamide solution p.o. (8 mg + 4 mg + 4 mg, 12 h and 2 h before, and 7 h after the start of the recording). RESULTS: Twenty-four-hour oesophageal acid exposure and the number of reflux episodes/hour were similar under the two experimental conditions: a median (IQ range) of 6.2% (3.3%-11.0%) of the time at pH < 4 and 2.6 (1.6-3.5)/h during placebo versus 8.8% (3.7%-14.8%) and 2.8 (2.3-4.9)/h during loperamide (P = ns). Acid clearance time was also similar: 1.8 +/- 0.3 min versus 1.6 +/- 0.2 min (P = ns). CONCLUSIONS: Loperamide did not decrease GOR, thus suggesting that an opioid agonist may not be useful in the treatment of GOR disease.

Adult↗
PubMed2002

Preparation of poly(methacrylic acid-g-poly(ethylene glycol)) nanospheres from methacrylic monomers for pharmaceutical applications.

Nanospheres of poly(methacrylic acid-grafted-poly(ethylene glycol)) were prepared by solution/precipitation polymerization. As colloidal drug delivery carriers, they present unique properties that render them promising candidates for oral protein delivery. The polymerization was carried out in water and the resulting suspension was freeze-dried. As with many colloidal systems, the freeze-dried suspension showed strong agglomeration after drying. The effects of preparation conditions on the particle size and redispersion were investigated using photon correlation spectroscopy. Furthermore, the ability of different types and concentrations of stabilizers (cryoprotectants and steric stabilizers) in preventing this phenomenon was addressed. Pluronics, block copolymers widely used as nonionic surfactants, were the most effective in stabilizing the particles during the freeze-drying process. Pluronic P123, however, increased significantly the particle size of the nanospheres. On the other hand, lyophilizates obtained in the presence of Pluronic F68 had good redispersion properties and no change in particle size was observed.

Drug Compounding↗
PubMed2002

Caffeine microparticles for nasal administration obtained by spray drying.

This study investigated the possibility to use spray drying technique to prepare powders formulations containing caffeine intended for nasal delivery. Spray dried powders containing caffeine and excipients, as filler and shaper agents, were prepared. Powders were investigated for particle size, morphology and delivery properties from Monopowder P nasal insufflator, assessing the influence of each excipient on microparticles characteristics. The results showed that the excipients strongly affected microparticle properties. Size, shape and agglomeration tendency are relevant characteristics of spray dried nasal powder.

Administration, Intranasal↗
PubMed2002

Influence of layer position on in vitro and in vivo release of levodopa methyl ester and carbidopa from three-layer matrix tablets.

A versatile oral controlled release system for the simultaneous delivery of levodopa methyl ester and carbidopa, consisting of a three-layer matrix tablet, has been studied and developed. Each individual layer of the matrix exhibited a different release mechanism, i.e. the first layer was swellable (S), the second one was erodible (E) and the third one was disintegrating (D). The three layers have been assembled in the monolithic matrix in different relative positions. It was found that in the monolith the three layers could interact, producing in vitro release profiles depending on their relative position. The monoliths having the configurations DSE and SDE were administered to human volunteers in order to determine the plasma profiles. The pharmacokinetic data showed a significant difference between the early time plasma curves: the monolith DSE, having the fast release profile, gave rise to a rapid appearance of a high levodopa plasma level, whereas the slower releasing monolith SDE produced a smoothed plasma concentration profile.

Administration, Oral↗
PubMed2002

Long-term effects of pneumatic dilatation on symptoms and lower oesophageal sphincter pressure in achalasia.

BACKGROUND: Pneumatic dilatation is an effective treatment for achalasia. Although follow-up studies have shown that its clinical benefit persists for years, it is still unknown whether the decrease in lower oesophageal sphincter (LOS) pressure is maintained over time. Our aim is to assess the long-term effects of pneumatic dilatation on symptoms and LOS pressure in patients with idiopathic achalasia. METHODS: Eleven consecutive patients with achalasia (7 men) underwent I (n = 5) or 2 (n = 6) pneumatic dilatations (Rigiflex dilator) in order to achieve a stable (>1 year) clinical remission. Clinical scores (0-12, with scores of <3 indicating remission) and LOS pressure (sleeve manometry) were determined before treatment, after 3 and 12 months, and then every year for 6 years. RESULTS: No operative complications occurred. The patients showed a marked clinical improvement (2.0 (2.0-2.0), median (IQ range), after 3 months versus 8.0 (7.2-9.0) before treatment; P < 0.001), which was maintained throughout the follow-up period. Concurrently, there was a marked decrease in LOS pressure (5.0 (4.0-7.0) mmHg after 3 months versus 25.0 (20.0-36.2) before treatment; P < 0.001), which also remained stable over time. CONCLUSIONS: One or two pneumatic dilatations induce stable clinical remission and a decrease in LOS pressure that remains unchanged over time. Our data further support the use of dilatations as first-line treatment of achalasia.

Adult↗
PubMed2002

Effect of calories and fat on postprandial gastro-oesophageal reflux.

BACKGROUND: Gastro-oesophageal reflux (GOR) is commonly considered to be worsened by fatty food, but it has recently been shown that changing the fat content of equicaloric meals has no effect on GOR over a 3-h postprandial period. Our aims were to verify this finding over a longer postprandial period and test the hypothesis that increasing the caloric content of balanced meals increases GOR. METHODS: Thirteen healthy subjects (6 men) aged 19-31 years underwent 6-h oesophageal pH monitoring after 3 solid/liquid meals of the same volume and osmolarity eaten on separate days in a randomized order: a) high fat (58% fat) 2.8 MJ; b) balanced (23% fat) 2.8 MJ; and c) balanced low calorie (25% fat) 1.6 MJ. RESULTS: The mean percentage of time at pH < 4 and the mean number of reflux episodes after the balanced 2.8 MJ meal (3.0% and 11.5. respectively) were higher (P < 0.05) than after the balanced 1.6 MJ meal (1.6% and 7.2) and similar to those after the equicaloric (2.8 MJ) high-fat meal (2.5% and 9.3). Acid clearance time was similar after all three meals. CONCLUSIONS: Our data suggest that advice on dietary habits in patients with GOR disease should be concentrated on decreasing the caloric load of meals rather than their fat content.

Adult↗
PubMed2002

Knowledge and opinion on prostate and prevalence of self-reported BPH and prostate-related events. A cross-sectional survey in Italy.

Benign prostatic hyperplasia (BPH) is a very common condition in ageing men and causes considerable morbidity. Although great strides have been made recently, important issues remain under-researched and poorly understood. We have conducted a survey on a representative sample of Italian males to investigate the knowledge and opinion on prostate, to estimate the self-reported prevalence and intensity of BPH and LUTS (low urinary tract symptoms) and to evaluate the performance of the International Prostate Symptom Score (I-PSS) in a population-based sample. Trained interviewers administered a standardized questionnaire to a representative random sample of 671 Italian men aged 50 years and over, between May and June 2000. Univariate and multivariate statistical techniques were used to estimate the prevalence of relevant events, and the associations with selected variables. Only half of responders were able to identify the reason for prostate enlargement, less than one-third recently had spoken with a doctor, and only 8.6% had had a rectal examination. Further, 13.7% (95% confidence interval (CI) 11.1-16.3%) had ever been told they had BPH, with less than half of them receiving surgery for BPH. About 19% reported moderate-severe I-PSS. Both self-reported BPH and severe-moderate LUTS increased significantly with age ( -value <0.01). As to the I-PSS performance, we documented in a community-based sample that it is reliable and valid. Results of the multivariate analysis suggest that, in addition to age, a person's knowledge that they have BPH and a poor perception of health status are the main variables associated with the probability of moderate-severe LUTS. In conclusion, this community-based survey documents that Italian males have a poor knowledge and perception of prostate-related conditions and do not adequately care about them and, thus, do not seek medical attention. These facts notwithstanding, urological conditions such as BPH are common and may largely affect an individual's life. Our findings might help in the design and implementation of effective interventions to improve people's knowledge and understanding of prostate and change their attitudes towards medical care.

Adult↗
PubMed2002

Characterization of a surface modified dry powder inhalation carrier prepared by "particle smoothing".

Atomic force microscopy (AFM) was used to investigate drug-carrier interactions between beclometasone dipropionate (BDP) and a series of untreated and modified lactose surfaces. This quantitative information was correlated with bulk characterization methods and an in-vitro study. Modified lactose surfaces were prepared using a proprietary process referred to as "particle smoothing" to obtain smooth carrier surfaces with or without the presence of magnesium stearate. The engineering of lactose carrier surfaces using the particle smoothing process resulted in significant differences in surface morphology when compared with the "as supplied" starting material. The energy of separation, between BDP and lactose samples, determined by AFM suggested similar lognormal distributions with a rank decrease in median separation energy (e(0.5)) (26.7, 20.6 and 7.7 microJ for untreated, particle-smoothed and particle-smoothed with magnesium stearate, respectively). A series of in-vitro twin stage impinger studies showed good correlation with the AFM separation energy measurements. The mean fine particle dose increased for the two processed lactose samples, with a significant increase for the lactose processed with magnesium stearate, 102.0+/-16 microg compared with 24.2+/-10.7 microg for the untreated lactose. Thus, the AFM presents as a possible pre-formulation tool for rapid characterization of particle interactions.

Administration, Inhalation↗
PubMed2001

Molecular disorders in transitional vs. peripheral zone prostate adenocarcinoma.

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been shown to be mechanisms for tumor-suppressor gene inactivation in human oncogenesis. In our study, we examined LOH and MSI using 16 polymorphic markers of DNA for chromosomes 1, 3, 7, 8, 10 and 11. Microdissected tumor samples were isolated from 32 patients, representing 11 foci of incidentally discovered prostate cancer of the transitional zone (TZ), 12 prostate cancer of the peripheral zone (PZ) and 10 of high-grade PIN. We found loss of heterozygosity in the TZ group in 91% of informative cases (10/11) with al least 1 marker compared to 58% of cases (7/12) in PZ group and 70% of cases (7/10) in the HGPIN group. Chromosome 7 showed the highest rate of allelic loss in all 3 categories, with loss of 43% of loci in PIN, 37% in TZ tumors and 31% in PZ tumors. At chromosome 11, LOH was detected in 26% of loci in the TZ group, in 7% of loci in the PZ group and in 13% of loci in the PIN group. On chromosome 8, the PZ and HGPIN group showed allelic loss in 22% and 21% of loci, respectively, compared to 10% detected in the TZ group. The TZ group showed a significant higher rate of allelic instability compared to that observed in tumor samples from the peripheral zone: 73% of cases (8/11) showed genetic alterations (RER+ phenotype) in at least 4 loci analyzed compared to 8% and 10% in the PZ and HGPIN groups, respectively (p = 0.0006). These data suggest that transitional zone carcinoma and peripheral zone carcinoma display distinct and specific genetic alterations in different chromosomes. This diversity may help explain biologic and clinical differences between carcinomas arising in these distinct zones of the prostate. Also our results strongly suggest that the RER+ mutator phenotype could be linked to early development of transitional zone prostate carcinoma.

Adenocarcinoma↗
PubMed2001

Clinical and angiographic correlates of dobutamine-induced wall motion patterns after myocardial infarction.

The ability of different dobutamine-induced wall motion patterns to define the anatomic status of the infarct-related artery (IRA) was evaluated in 159 patients who underwent dobutamine stress echocardiography (DSE) and coronary angiography 10 +/- 2 and 18 +/- 3 days, respectively, after hospital admission. The DSE result was classified as: (1) biphasic: improvement with a low dose followed by deterioration with a high dose; (2) worsening: direct deterioration at low or high doses; (3) sustained improvement: improvement with a low dose that was maintained at high dose; and (4) no change: no change during the entire protocol. A diameter narrowing >70% (50% for the left main stem) of major coronary arteries indicated a severe lesion. Angiograms were classified according to the jeopardy score and collateral circulation graded according to Rentrop's classification. DSE was positive in 92 patients (22 had biphasic results and 70 had worsening results) and negative in 67 patients (14 had sustained improvement and 53 had no changes). Biphasic response was associated with more frequent anterior infarction (p <0.05) and higher resting (p <0.001) and peak (p <0.01) wall motion score indexes. The IRA was totally occluded in 4 of the 92 patients (4%) with positive (worsening pattern) and 12 of the 67 patients (18%) with negative (no change pattern) tests. The biphasic pattern was associated with the highest jeopardy score and was significantly (p <0.05) more specific (100%) compared with worsening (78%) in identifying a severe stenosis of the IRA. The combination of ischemic patterns provided a significantly superior sensitivity (p <0.0001). Logistic regression analysis identified the biphasic pattern as the only significant predictor. Conversely, the prediction of total occlusion of the IRA was poor. Sustained improvement was the most specific (100%) predictor of absence of severe stenosis of the IRA, whereas the combination with no change pattern provided a significantly superior sensitivity (p <0.0001). Thus, DSE effectively predicts the residual stenosis of the IRA. In particular, the biphasic response has an excellent specificity and positive predictive value and is the only significant predictor among clinical and echocardiographic variables.

Adrenergic beta-Agonists↗
PubMed2001

Translocation of drug particles in HPMC matrix gel layer: effect of drug solubility and influence on release rate.

The aim of this work was to study the release mechanisms of drugs having different solubility (buflomedil pyridoxalphosphate 65%, sodium diclofenac 3.1%, nitrofutantoin 0.02% w/v,) from hydroxypropyl methylcellulose (HPMC) matrices by concomitantly studying swelling, diffusion and erosion fronts movement and drug delivery. The main goal was to clarify the role played by polymer swelling in drug transport. The results showed that the rate and amount of drug released from swellable matrices was dependent not only from drug dissolution and diffusion but also from solid drug translocation in the gel due to polymer swelling. In fact, as drug solubility decreased, the slower drug dissolution rate in the gel layer allowed drug particles to be transported close to the matrix erosion front. The presence of solid particles in the gel reduced the swelling and the entanglement of polymer chains and affected the resistance of gel towards erosion. As a consequence, the matrix became more erodible. The erosive delivery accelerated after the matrix had been completely transformed into the rubbery state, particularly when a considerable amount of solid drug particles remained in the gel phase.

Diclofenac↗
PubMed2001

Design of triptorelin loaded nanospheres for transdermal iontophoretic administration.

Triptorelin is a decapeptide analog of luteinizing hormone releasing hormone, currently used for the treatment of sex-hormones dependents diseases. The aim of this work was to prepare triptorelin-loaded nanospheres useful for transdermal iontophoretic administration. Nanospheres were prepared with the double emulsion/solvent evaporation technique. The effect of three parameters on the encapsulation efficiency has been determined: the role of the pH of the internal and external aqueous phases, the nature of the organic solvent and the effect of three different poly(lactide-co-glycolide) (PLGA) co-polymers. Particle size, zeta potential and release kinetics were also determined. The encapsulation efficiency varied from 4 to 83% reaching the maximum value when both the internal and the external water phases were brought to pH 7 (isoelectric point of the peptide), methylene chloride was used as solvent of the copolymers and PLGA rich in free carboxylic groups was employed. The release profiles obtained with this co-polymer were characterized by the absence of burst effect. This behavior as well as the high encapsulation efficiency was explained by an ionic interaction occurring between the peptide and the co-polymer. This supports the already expressed theory that the release of peptides and proteins from PLGA nanospheres is also governed by the affinity of the encapsulated molecule versus the polymer. The obtained nanoparticles, regarding their size, amount encapsulated and zeta potential, were shown to be suitable for transdermal iontophoretic administration.

Administration, Cutaneous↗
PubMed2001

Plasma and skin concentration of 5-methoxypsoralen in psoriatic patients after oral administration.

The aim of this work was to investigate the distribution of 5-methoxypsoralen in the skin after oral administration of the drug and to examine the correlation between skin and plasma concentrations. 5-Methoxypsoralen skin concentration was measured in both healthy and psoriatic sites of 10 psoriatic patients after single and multiple oral doses. The results obtained show that 5-methoxypsoralen accumulates at higher levels in the more external layers of the skin after oral administration. The high affinity of drug for the stratum corneum was confirmed by in vitro skin affinity measurements. The concentration of 5-methoxypsoralen in the skin was similar in both psoriatic and healthy sites, indicating that the pathology does not influence drug distribution in the skin. After single dose administration, a linear correlation was found between skin and plasma drug concentration. After multiple dose administration, drug concentration in the skin was fairly constant despite the variable plasma concentrations in different subjects.

5-Methoxypsoralen↗
PubMed2001

Androgen secretion in ectopic ACTH syndrome and in Cushing's disease: modifications before and after surgery.

The role of ACTH in the control of adrenal androgen secretion is known, although the possible existence of other regulatory factors has been also suggested. While some data concerning Cushing's disease have been reported, only few studies concerned androgen levels in ectopic ACTH secretion. The aim of this study was to evaluate serum DHEA-S, androstenedione (A) and testosterone (T) levels in 36 women with ACTH-dependent Cushing's syndrome (30 with Cushing's disease and 6 with ectopic ACTH secretion) before and after surgery. Two men with ectopic ACTH production were also studied. In 30 women with Cushing's disease serum DHEA-S (9.6 +/- 0.9 micromol/l), A (15.2 +/- 1.2 nmol/l) and T (4.1 +/- 0.5 nmol/l) were higher than in controls (p < 0.01): elevated DHEA-S, A and T values were found in 8, 18 and 17 cases, respectively. After adenomectomy in 15 apparently cured patients DHEA-S, A and T levels were low at 1 - 3 months and at 6 - 12 months after surgery. At 18 - 24 months, DHEA-S remained low in spite of cortisol normalisation. In ectopic Cushing's syndrome, A levels were significantly higher (23.1 +/- 4.9 nmol/l) than in Cushing's disease (p < 0.05), while no differences were found in DHEA-S and T levels. Two patients had elevated DHEA-S values, 3 women had high T levels and 7 of the 8 patients had very high A concentration that was lowered in 3 operated cases. In conclusion, the pattern of adrenal androgen secretion is rather different in patients with pituitary or with ectopic Cushing's syndrome. While the frequency of DHEA-S and T alterations is similar, androstenedione secretion is greatly increased in the latter condition. It is suggested that in ACTH-secreting non-pituitary tumours, the production of a POMC-derived peptide, although unidentified, may lead to preferentially stimulated androstenedione secretion, without affecting other enzymatic pathways.

ACTH Syndrome, Ectopic↗
PubMed2001

Macrocryosectioning of the prostate: a simple technique.

Whole mount sections of the prostate are widely used in many laboratories. Macrocryosections of the gland; that is, whole mount frozen sections of the prostate from radical prostatectomies represent a useful new research protocol. The technique is very simple and does not require expensive equipment.

Cryoultramicrotomy↗