Hamartoma of the breast in a young woman. Case report.

Hamartoma is a benign tumor-like malformation characterized by a focal mixture of mature cells and tissues normally present in affected area. The hamartoma of the breast is rare. We report a case in an asymptomatic young woman coming to our attention for a left breast lesion detected by ultrasound screening.

[Diagnostic and surgical problems of ectopic breast cancer]. / Problemi diagnostici e chirurgici del carcinoma nella mammella in sede atipica.

Cancer of supernumerary breast or ectopic breast tissue has haigher incidence than the cancer on ortotopic breast. This finding puts some problems about the diagnosis and therapy of ectopic breast cancer. The Authors describe their personal experience in three patients surgically treated and discuss about problems and solutions of this pathology.

[Advantages and limits of tumescent anesthesia in outpatient surgery]. / Vantaggi e limiti dell'anestesia per tumescenza in chirurgia ambulatoriale.

The Authors report the results of the tumescent anesthesia in 187 patients submitted to various outpatient surgical procedures comparing with those in patients submitted to local anesthesia by direct infiltration.

Resultados de 5 anos da cirurgia bariátrica em pacientes com obesidade e hipertensão. Um estudo clínico randomizado / 5-year results of bariatric surgery in patients with obesity and hypertension. A randomized clinical trial

INTRODUÇÃO: Dados de estudos randomizados avaliando os efeitos a longo prazo da cirurgia bariátrica no controle e remissão da hipertensão (HTN) são escassos. O seguimento de curto e médio prazo do Estudo GATEWAY (1 e 3 anos) mostrou melhora significativa e remissão da hipertensão após a cirurgia bariátrica. Aqui, apresentamos os dados de acompanhamento de 5 anos deste estudo. MÉTODOS: Conduzimos um ensaio clínico randomizado, em um centro único, fase III, paralelo e aberto. Pacientes com obesidade graus 1 e 2, tomando no mínimo 2 medicamentos anti-hipertensivos em doses máximas para hipertensão, foram alocados aleatoriamente para Bypass gástrico em Y de Roux (RYGB) combinado com tratamento clínico (TC) ou TC (estilo de vida/aconselhamento nutricional) isoladamente. O desfecho primário foi a redução de pelo menos 30% do total de anti-hipertensivos, mantendo níveis controlados de pressão arterial (PA)<140/90mmHg. A análise principal seguiu o princípio de intenção de tratar modificada e os valores ausentes foram imputados com a técnica de imputação múltipla. Os desfechos secundários incluíram vários biomarcadores. RESULTADOS: Foram incluídos 100 pacientes (76% mulheres, idade: 43,8±9,2 anos, índice de massa corporal, IMC: 36,9±2,7Kg/ m2). Após 5 anos, o IMC foi de 27,8±3,8kg/m2 para RYGB e 36,4±3,9kg/m2 para TC (P<0,001). 82,7% dos pacientes do grupo RYGB atingiram o desfecho primário, enquanto no grupo TC foram 14,7% (rate ratio 5,6 [95% CI]: 2,8 a 11,1; P<0,001) (Fig. A). A mediana (IQR) de número de drogas foi 1 (0-1) e 3 (3-4) para RYGB e TC, respectivamente. As taxas de remissão da hipertensão foram de 46,4 e 2% para RYGB e TC (Fig. B), respectivamente (P<0,001); A análise de sensibilidade considerando apenas os casos com seguimento concluído (n=69) revelou resultados consistentes. Os desfechos secundários nos grupos RYGB e TC, aos 60 meses, foram: circunferência abdominal 88,05 ± 9,84cm e 109,44 ± 9,76cm (P<0,001) ; hemoglobina glicada 5,4 ± 0,43% e 5,96 ± 0,9% (P<0,001) ; insulina 6,41 ± 2,46mU/L e 24,65 ± 16,57mU/L (P<0,001) ); LDL colesterol 93.61 ± 31.06mg/dL e 109.94 ± 37.58mg/dL (P=0,022); triglicerídeos 86,76 ± 38,45mg/dL e 140,33 ± 59,11 mg/dL (P<0,001); proteína C reativa de alta sensibilidade 0,81 ± 0,76mg/L e 6,13 ± 6,22mg/L (P=0,005), respectivamente. CONCLUSÕES: A cirurgia bariátrica é uma estratégia eficaz e duradoura no controle da PA com menor número ou nenhum medicamento anti-hipertensivo e na melhora do perfil metabólico e inflamatório em pacientes com obesidade graus 1 ou 2 e hipertensão.

[Cutaneous B-cell non-Hodgkin lymphoma: clinical aspects, diagnostic and surgical approach]. / Linfoma cutaneo non Hodgkin a immunofenotipo B: clinica, orientamento diagnostico e chirurgico.

By clinical observation and surgical treatment of a patient with cutaneous B-cell non-Hodgkin lymphoma, the Authors describe the nosological approach, the correct diagnosis and the surgical treatment in this disease.

Resultados de 5 anos da cirurgia bariátrica em pacientes com obesidade e hipertensão. um estudo clínico randomizado / 5-year outcomes of bariatric surgery in patients with obesity and hypertension. a randomized clinical trial

INTRODUÇÃO: Dados de estudos randomizados avaliando os efeitos a longo prazo da cirurgia bariátrica no controle e remissão da hipertensão (HTN) são escassos. O seguimento de curto e médio prazo do Estudo GATEWAY (1 e 3 anos) mostrou melhora significativa e remissão da hipertensão após a cirurgia bariátrica. Aqui, apresentamos os dados de acompanhamento de 5 anos deste estudo. MÉTODOS: Conduzimos um ensaio clínico randomizado, em um centro único, fase III, paralelo e aberto. Pacientes com obesidade graus 1 e 2, tomando no mínimo 2 medicamentos anti-hipertensivos em doses máximas para hipertensão, foram alocados aleatoriamente para Bypass gástrico em Y de Roux (RYGB) combinado com tratamento clínico (TC) ou TC (estilo de vida/aconselhamento nutricional) isoladamente. O desfecho primário foi a redução de pelo menos 30% do total de anti-hipertensivos, mantendo níveis controlados de pressão arterial (PA) <140/90mmHg. A análise principal seguiu o princípio de intenção de tratar modificada e os valores ausentes foram imputados com a técnica de imputação múltipla. Os desfechos secundários incluíram vários biomarcadores. RESULTADOS: Foram incluídos 100 pacientes (76% mulheres, idade: 43,8±9,2 anos, índice de massa corporal, IMC: 36,9±2,7Kg/ m2). Após 5 anos, o IMC foi de 27,8±3,8kg/m2 para RYGB e 36,4±3,9kg/m2 para TC (P<0,001). A análise de sensibilidade considerando apenas os casos com seguimento concluído (n=69) revelou resultados consistentes. Os desfechos secundários nos grupos RYGB e TC, aos 60 meses, foram: circunferência abdominal 88,05 ± 9,84cm e 109,44 ± 9,76cm (P<0,001) ; hemoglobina glicada 5,4 ± 0,43% e 5,96 ± 0,9% (P<0,001); insulina 6,41 ± 2,46mU/L e 24,65 ± 16,57mU/L (P<0,001); LDL colesterol 93.61 ± 31.06mg/dL e 109.94 ± 37.58mg/dL (P=0,022); triglicerídeos 86,76 ± 38,45mg/dL e 140,33 ± 59,11 mg/dL (P<0,001); proteína C reativa de alta sensibilidade 0,81 ± 0,76mg/L e 6,13 ± 6,22mg/L (P=0,005), respectivamente. CONCLUSÕES: A cirurgia bariátrica é uma estratégia eficaz e duradoura no controle da PA com menor número ou nenhum medicamento anti-hipertensivo e na melhora do perfil metabólico e inflamatório em pacientes com obesidade graus 1 ou 2 e hipertensão.

Designing novel pH-sensitive non-phospholipid vesicle: characterization and cell interaction.

In this work, we report the preparation, the characterization and interaction with cells of novel pH-sensitive non-phospholipid vesicle formulations, from a non-ionic surfactant mixed with cholesterol (CHOL) and his derivative cholesteryl hemisuccinate (CHEMS), as pH-sensitive molecule. This molecule, can destabilize the vesicle lipid bilayer when exposed to an acidic environment, with a subsequent release of vesicular content, enhancing the cytoplasmatic delivery of drugs to target cells. Vesicles were characterized by static and dynamic light scattering, in order to evaluate their dimensions, bilayer thickness and vesicle stability. Membrane permeability changes were determined by the release of entrapped hydroxypyrene-1,3,6-trisulfonic acid (HPTS). Also diphenylhesatriene (DPH) fluorescence anisotropy and zeta potential measurements were used to evidence the pH sensitivity. Furthermore vesicles were characterized by means of electronic microscopy after freeze-fracture. The interaction of non-lipid vesicles containing different fluorescent dyes with Raw 264.7, mouse monocite macrophage, were analyzed by flow cytometric analysis. The obtained results indicate that the pH-sensitive vesicular structures show good plasma stability and relevant pH-sensitivity. Moreover this formulation was able to interact with target membranes (i.e. plasma or endosomal membrane) and to release the encapsulated material into the cytoplasm.

Novel O-palmitoylscleroglucan-coated liposomes as drug carriers: development, characterization and interaction with leuprolide.

Polysaccharide-coated liposomes have been studied for their potential use for peptide drug delivery by the oral route because they are able to minimize the disruptive influences on peptide drugs of gastrointestinal fluids. The aim of this work was to synthesize and characterize a modified polysaccharide, O-palmitoylscleroglucan (PSCG), and to coat unilamellar liposomes for oral delivery of peptide drugs. To better evaluate the coating efficiency of PSCG, also scleroglucan (SCG)-coated liposomes were prepared. We studied the surface modification of liposomes and the SCG- and PSCG-coated liposomes were characterized in terms of size, shape, zeta potential, influence of polymer coating on bilayer fluidity, stability in serum, in simulated gastric and intestinal fluids and against sodium cholate and pancreatin. Leuprolide, a synthetic superpotent agonist of luteinizing hormone releasing hormone (LHRH) receptor, was chosen as a model peptide drug. After polymer coating the vesicle dimensions increased and the zeta potential shifted to less negative values. These results indicate that both SCG- and PSCG-coated liposomes surface and DSC results showed that PSCG was anchored on the liposomal surface. The stability of coated-liposomes in SGF, sodium cholate solution and pancreatin solution was increased. From this preliminary in vitro studies, it seems that PSCG-coated liposomes could be considered as a potential carrier for oral administration.

Direct determination by capillary electrophoresis of cardiovascular drugs, previously included in liposomes.

The lipophilicity of some cardiovascular drugs was determined by capillary electrophoresis (CE). Mexiletine, amlodipine and indapamide, the drugs considered, were in contact with liposomial vescicles for 2, 4 or 6 h. After the contact time the drugs, penetrated into liposomial vesicles, were determined by CE using phosphate buffer (pH 6.3 or 7.4) or borate buffer (pH 9). The lipophilicity of three drugs was determined considering the drug percentage penetrated into liposomial vesicles. The found lipohilicity order was amlodipine > mexiletine > indapamide.

Gellan in sustained release formulations: preparation of gel capsules and release studies.

The ability of gellan to form gels in the presence of calcium ions enabled us to prepare capsules by gelation of this polysaccharide around a core containing starch, calcium chloride and a model drug. Release from the dried capsules was studied in vitro by means of the rotating basket technique (USP) in different environmental conditions (distilled water, pH = 2.0, pH = 6.8) and the effects of the presence of increasing amounts of drug in the formulation were also investigated. The behaviour of the gellan capsules was compared with that of beads prepared with the same polysaccharide but containing different additives. Results obtained indicate that gellan is suitable for the formulation of sustained release capsules and that solvent uptake by the dried capsules is most likely the main factor capable of affecting the rate of delivery from the tested preparations.

New vesicular ampicillin-loaded delivery systems for topical application: characterization, in vitro permeation experiments and antimicrobial activity.

In this paper, the experimental conditions for preparing ampicillin-loaded surfactant vesicles (SVs) are described. Our studies are focused on the potential use of a vesicular polymeric dispersion as ampicillin delivery system for topical application. The main components of the formulation are uncharged and charged SVs loaded with ampicillin and dispersed in a gellan solution. The following issues are addressed: the drug encapsulation efficiency (e.e.), the kinetic of drug release from the delivery systems, the antimicrobial activity of vesicle-entrapped ampicillin. The in vitro permeation experiments through a synthetic lipophilic barrier (Silastic) and through porcine skin are carried out to evaluate the potential use as a dermal formulation. The use of both a synthetic and a biological membrane allows to discriminate between the effects related to variations of thermodynamic parameters and those correlated to biological factors. The release rate of ampicillin is increased by encapsulation in neutral and negatively charged SVs and the permeation rate was slowed by dispersion of drug-loaded SVs in gellan solution. Finally, studies of antimicrobial activity on prepared systems evidenced that ampicillin encapsulated in SVs exhibit a higher activity than the free drug.

Novel hydrogel system from scleroglucan: synthesis and characterization.

New hydrogels obtained by a crosslinking reaction between the polycarboxylated derivative of scleroglucan (sclerox) and 1, 6-hexanedibromide have been prepared and characterized. Different ratios between the alkane dihalide and sclerox yielded products with appreciably different properties. Water uptake by the hydrogel with a low degree of crosslinking was remarkably affected by ionic strength. The diffusion of a model molecule (theophylline) through the swelled crosslinked polymers was studied and the theoretical analysis leading to the calculation of permeability coefficients in different environmental conditions is reported. Tablets prepared with one of the new hydrogels behaved as swellable monolithic systems suitable for sustained drug release.

Clinical evaluation methods for posterior composite restorations.

Two methods of evaluating the in vivo wear of posterior composite restorations are described and compared with the USPHS direct clinical evaluation system. The three methods were consistent among themselves and over the two years of the study. In order of increasing sensitivity, the methods were: USPHS, total ranking of models, and categorizing of models according to a set of standards. The last procedure identified statistically significant differences (p less than 0.05) between the composite formulations as early as the nine-month recall. All formulations experienced increasing wear with time, but at a decreasing rate.

Prevention of molecular self-association by sodium salicylate: effect on insulin and 6-carboxyfluorescein.

The effect of sodium salicylate on the concentration-dependent self-association of insulin and 6-carboxyfluorescein (CF), as expressed by metachromasy, fluorescence, and changes in aqueous solubility, was learned. By decreasing the CF concentration from 12 to 0.48 microgram.ml-1, lambda max peaks shift from the shorter wavelengths (451, 474 nm), indicating the presence of oligomers, toward the monomer wavelength region (484 nm). Sodium salicylate shifts the peaks of a 12 micrograms.mL-1 CF solution towards the monomer region, eliminating the peak at the lower wavelengths and generating a spectrum with one peak at 490 nm, the effect being concentration dependent. The fluorescence of insulin and CF solutions increases with their concentration. Quenching of these solutions was observed, up to complete elimination of fluorescence, when various concentrations of salicylate were added. The water solubility of both molecules, CF and insulin, was considerably increased with the addition of increasing concentrations of salicylate to the solutions: at 37 degrees C, 2.5 M sodium salicylate solution increases the CF solubility 532 times from 12.2 to 6.5 mg.mL-1, and 1.5 M salicylate increases the solubility of insulin 7875 times, thus an aqueous solution containing 630 mg.mL-1 of insulin may be prepared. The results obtained here, together with our previously reported data, indicate that the interference between sodium salicylate and drug self-association behavior, by increasing drug solubility, may substantially contribute to the improved drug bioavailability mediated by salicylate.

Treatment of periodontitis by local administration of minocycline microspheres: a controlled trial.

BACKGROUND: Periodontitis is an inflammatory condition of tooth-supporting tissues that is usually treated by mechanical removal of plaque and microorganisms that adhere to teeth. This treatment, known as scaling and root planing, is not optimally effective. Adjunctive therapy with locally delivered antimicrobials has resulted in improved clinical outcomes such as probing depth reduction. This article reports on the efficacy and safety of locally administered microencapsulated minocycline. METHODS: Seven hundred forty-eight (748) patients with moderate to advanced periodontitis were enrolled in a multi-center trial and randomized to 1 of 3 treatment arms: 1) scaling and root planing (SRP) alone; 2) SRP plus vehicle; or 3) SRP plus minocycline microspheres. The primary outcome measure was probing depth reduction at 9 months. Clinical assessments were performed at baseline and 1, 3, 6, and 9 months. RESULTS: Minocycline microspheres plus scaling and root planing provided substantially more probing depth reduction than either SRP alone or SRP plus vehicle. The difference reached statistical significance after the first month and was maintained throughout the trial. The improved outcome was observed to be independent of patients' smoking status, age, gender, or baseline disease level. There was no difference in the incidence of adverse effects among treatment groups. CONCLUSIONS: Scaling and root planing plus minocycline microspheres is more effective than scaling and root planing alone in reducing probing depths in periodontitis patients.

Lidocaine-loaded non-ionic surfactant vesicles: characterization and in vitro permeation studies.

Our research on topical application of lidocaine-loaded non-ionic surfactant vesicles (NSVs) was prompted by the great interest on new delivery systems for local anaesthetics. This study is focused on a novel formulation of NSVs entrapping lidocaine in the form of a free base (LID) and a hydrochloride (LIDHCl). NSVs were prepared from polyoxyethylene sorbitan monolaurate (Tween20) and cholesterol. The effect of vesicle composition and environmental pH condition (8.6-5.5) on drug encapsulation efficiency (e.e.) was investigated. Experimental strategies involved: freeze-fracture, microscopy technique, dynamic light scattering, permeation through Silastic and mouse abdominal skin, in vitro release kinetics of vesicle-entrapped drugs, fluorescence quenching analyses. Diffusion experiments showed that the flux of charged lidocaine through Silastic membrane was possible only after the vesicle encapsulation. Permeation through mouse abdominal skin of LIDHCl loaded vesicles showed a higher flux and a shorter lag time with respect to classical liposome formulations, while LID permeation rate was quite similar for NSV and liposome formulations. Vesicles were also prepared in the presence of dicetylphosphate (DCP) and N-cetylpyridinium chloride (CP) to obtain negatively and positively charged vesicles respectively, but in this case the e.e. of the drug was negligible. The possible reason of the remarkable lower e.e. observed with charged vesicles was investigated by means of fluorescence quenching experiments.

Model lipophilic formulations of retinyl palmitate: influence of conservative agents on light-induced degradation.

Vitamin A is widely employed in pharmaceuticals and cosmetics. The all-trans (AT) isomer (100% of biological potency) is sensible to different factors, such as light, heat and formulation components, leading to its degradation or isomerization. The main objective of this work was to study, in model cosmetic lipophilic vehicles, the degradation of retinyl palmitate (RetP) to the less active cis-isomers in presence of widely used conservative agents (propyl gallate and Vitamin E). Two lipophilic phases were used (liquid paraffin and almond oil) because liquid paraffin, almost composed of satured hydrocarbons, is not degraded by light exposure, while almond oil, containing several double bonds, could interfere with light-induced degradative process of RetP. In the first phase, the more suitable analytical method was chosen between normal and reverse phase HPLC to follow the degradation of RetP. In the second phase, RetP light-induced degradation was studied to simulate storage condition effect on cosmetic products ageing. The results showed that: (a) the reverse phase HPLC technique, unable to separate the all-trans from the 13-cis and 9-cis isomers, derived by Vitamin A isomerization, leads to an incorrect quantitation of RetP; (b) the lipophilic vehicle influences the isomerization-degradation process; (c) the conservative agents do not protect from degradation.

Cholic acids/salts as barriers to diffusing species: effect of pH.

Bile acids have been absorbed on a microporous polypropylene membrane and the diffusion of ionic and non-ionic compounds through the barriers obtained has been studied at different pH values. Results indicate that permeation rates are affected by environmental pH conditions and an explanation of this behaviour is proposed. This study represents an approach for a pH-controlled drug delivery system.

A possible pH-controlled drug delivery system based on a derivative of the polysaccharide scleroglucan.

Four carboxylated derivatives of scleroglucan have been obtained by oxidation, to different extents, of the glucopyranose side chains of the natural polysaccharide. The diffusion of model molecules through aqueous solutions of these new products was measured at various pH values. The reversible pH induced sol-gel transition of some of the polyelectrolyte solutions tested effects a remarkable variation in the diffusion rate of the permeating species; in this sense the most interesting polysaccharide appears to be the product with 70% oxidized glucopyranose moieties. The behaviour of scleroglucan and its derivatives has been compared with that of carboxymethylcellulose and the mechanism involved in drug permeation and release discussed. The possible application of one of the new products in controlled release formulations for oral use is also reported.

A polymeric film responding in diffusion properties to environmental pH stimuli: a model for a self-regulating drug delivery system.

A new polymeric film, ethylene-vinyl-NN-diethylglycinate random copolymer, has been studied to evaluate possible applications of such a material to produce controlled release dosage forms. Protonation of the substituted amino groups took place to different extents according to environmental pH conditions. The polymeric film proved to be permeable only to uncharged species, the rate of diffusion of which increased with the increasing charge of the membrane. This effect might be related to strong polymer-proton interactions affecting structure and transport properties of the film and enhancing the solvation process. The charged form of a number of barbituric acid derivatives did not diffuse through the membrane. The uncharged forms permeated the polymeric sheeting at rates consistent with their partition coefficients and which increased with the increasing charge of the polymer.