Encapsulation of Liposomes within pH Responsive Microspheres for Oral Colonic Drug Delivery.

A novel liposome-in-microsphere (LIM) formulation has been created comprising drug-loaded liposomes within pH responsive Eudragit S100 microspheres. The liposomes contained the model drug 5-ASA and were coated with chitosan in order to protect them during encapsulation within the microspheres and to improve site-specific release characteristics. In vitro drug release studies showed that LIMs prevented drug release within simulated stomach and small intestine conditions with subsequent drug release occurring in large intestine conditions. The formulation therefore has potential for oral colonic drug delivery.

Evaluation of liposomes coated with a pH responsive polymer.

Liposomes have been coated with the pH responsive polymer, Eudragit S100, and the formulation's potential for lower gastrointestinal (GI) targeting following oral administration assessed. Cationic liposomes were coated with the anionic polymer through simple mixing. The evolution of a polymer coat was studied using zeta potential measurements and laser diffraction size analysis. Further evidence of an association between polymer and liposome was obtained using light and cryo scanning electron microscopy. Drug release studies were carried out at pH 1.4, pH 6.3 and pH 7.8, representing the pH conditions of the stomach, small intestine and ileocaecal junction, respectively. The polymer significantly reduced liposomal drug release at pH 1.4 and pH 6.3 but drug release was equivalent to the uncoated control at pH 7.8, indicating that the formulation displayed appropriate pH responsive release characteristics. While the coating layer was not able to withstand the additional challenge of bile salts this reinforces the importance of evaluating these types of formulations in more complex media.

Resultados de la introducción del “live” CD, sobre la dispensación de medicamentos y productos sanitarios en la farmacia comunitaria, en la enseñanza de la legislación farmacéutica / Results of the introduction of "live" CD, on the dispensing of medicines and medical devices in the community pharmacy in the teaching of pharmaceutical legislation

Se presentan los resultados de la introducción de un CD interactivo sobre la dispensación demedicamentos y productos sanitarios en farmacias comunitarias para los estudiantes que terminan susestudios de farmacia. Los alumnos valoran la aplicación práctica del “Live” CD, lo que se ha podidocomprobar mediante una encuesta. El objetivo de la utilización de esta herramienta de trabajo es elfacilitar que los alumnos se introduzcan en el ámbito de la regulación farmacéutica de una formapráctica y que valoren los conocimientos teóricos de la asignatura como una necesidad en una parte dela actividad profesional y que complementa al resto de conocimientos y habilidades impartidas enotras asignaturas de la carrera.La prueba piloto se ha llevado a cabo con los alumnos que han optado por la evaluación continuadacon objeto de valorar si esta herramienta de trabajo facilita el aprendizaje y rendimiento de losresultados del alumnado. Se ha constatado que se han obtenido mejores resultados en los alumnos quehan utilizado este medio(AU)

We present the results of the introduction of an interactive CD on dispensing drugs and medicaldevices in community pharmacies for students graduating in pharmacy. We have been able todemonstrate through a survey that students can see the practical application of the Live CD, whichhelps them to see the subject of Law and Ethics as practical and not so far away from the knowledgethat they expect to acquire when they join the college. Moreover, the academic performance ofstudents who opted for continuous assessment, which involved working with the CD, has been betterthan those who opted for the single assessment(AU)

Intragastric balloon for weight loss: results in 100 individuals followed for at least 2.5 years.

BACKGROUND AND STUDY AIMS: To determine long-term outcome after treatment with an intragastric balloon for 6 months, with no structured weight maintenance program offered after balloon removal. PATIENTS AND METHODS: 100 consecutive overweight/obese individuals (mean body mass index [BMI] 35.0 +/- 5.6 kg/m (2)) were prospectively followed after endoscopic implantation of a saline-filled intragastric balloon; 97 completed final follow-up at a mean of 4.8 +/- 1.6 years. Successful intragastric balloon therapy was defined as weight loss at 6 months of > or = 10 % of weight at baseline, that remained > or = 10 % until 2.5 years, without bariatric surgery. All analyses followed intention-to-treat principles. RESULTS: At 6 months, mean weight loss was 12.6 +/- 8.3 kg, 63 individuals had > or = 10 % baseline weight loss; no severe morbidity was detected. During the first and second years following intragastric balloon removal, mean body mass increased by 4.2 +/- 6.8 and 2.3 +/- 6.0 kg, respectively ( P < 0.001 for both year-on-year comparisons). At 2.5 years, intragastric balloon therapy had been successful in 24 participants. At final follow-up (4.8 +/- 1.6 years), 28 had > or = 10 % baseline weight loss, 35 had undergone bariatric surgery (60 % had preoperative mass higher than baseline), and 3 were lost to follow-up; the 34 remaining had lost 1.5 +/- 5.8 kg compared with baseline. During follow-up, 13 had a second intragastric balloon implanted and 13 took sibutramine for short periods. CONCLUSION: Intragastric balloon therapy was relatively innocuous and associated with successful weight loss and maintenance at 2.5 years in a quarter of participants. It represents a valid option for weight loss.

Feasibility of adequate resectable rectal cancer treatment in a third-level hospital.

PURPOSE: The aim of this study was to determine the feasibility, concerning compliance to protocol and recommended clinical practice guidelines, as well as efficacy results of multidisciplinary treatment (surgery, radiotherapy and chemotherapy) of resectable rectal cancer in a third-level hospital devoid of radiotherapy and clinical oncology units. PATIENTS AND METHODS: A retrospective, single-institution analysis was completed for 45 consecutive patients diagnosed with resectable rectal cancer who entered an officially proposed multidisciplinary treatment protocol from October 1998 to September 2003. Adequacy of patient inclusion, according to clinical stage, was reviewed. Neoadjuvant radiotherapy schedule, surgery procedures and adjuvant chemotherapy indication were assessed. All treatment time intervals were analysed. Finally, efficacy results are discussed and contextualised by comparison with results of clinical trials which support this treatment strategy. RESULTS: According to an independent board review, 3 patients (6.7%) with stage I rectal cancer, 31 patients (68.9%) with stage II and 11 patients (24.4%) with stage III rectal cancer were included. Radiotherapy dosage, volume and schedule were as planned. Median time from diagnosis to start of radiotherapy was 26.36 days (24.26- 28.57; CI 95%). Median duration of radiotherapy was 6.00 days (5.56-6.44; CI 95%). Median time from start of radiotherapy to surgery was 15.67 days (14.47-16.87; CI 95%). Median time from completion of radiotherapy to surgery was 10.67 days (9.53-11.81; CI 95%). Most of the patients underwent low anterior resection [23 patients (51.2%)] and abdominoperineal resection [16 patients (35.6%)]. Correlation between clinical and pathologic staging was as expected. Twenty-nine patients (64.4%) of the 45 that were initially included started adjuvant chemotherapy. A statistically significant relationship between pathologic stage (grouped I-II vs. III) and the use of adjuvant chemotherapy was found (p=0.033; chi-square test). Radiotherapy- and chemotherapy-induced toxicity did not differ from that previously reported. With a median follow-up of 65.46 months, a total of 10 recurrences have been diagnosed, all of them in stage III patients. Overall survival rate at five years was 76% for the complete population included. CONCLUSION: Multidisciplinary treatment of resectable rectal cancer in a third-level hospital is feasible. Although efficacy results are comparable to those previously reported in the literature, further improvements in clinical staging as well as in adjuvant chemotherapy indication are desirable.

Feasibility of adequate resectable rectal cancer treatment in a third-level hospital

PURPOSE: The aim of this study was to determine the feasibility, concerning compliance to protocol and recommended clinical practice guidelines, as well as efficacy results of multidisciplinary treatment (surgery, radiotherapy and chemotherapy) of resectable rectal cancer in a third-level hospital devoid of radiotherapy and clinical oncology units. PATIENTS AND METHODS: A retrospective, single-institution analysis was completed for 45 consecutive patients diagnosed with resectable rectal cancer who entered an officially proposed multidisciplinary treatment protocol from October 1998 to September 2003. Adequacy of patient inclusion, according to clinical stage, was reviewed. Neoadjuvant radiotherapy schedule, surgery procedures and adjuvant chemotherapy indication were assessed. All treatment time intervals were analysed. Finally, efficacy results are discussed and contextualised by comparison with results of clinical trials which support this treatment strategy. RESULTS: According to an independent board review, 3 patients (6.7%) with stage I rectal cancer, 31 patients (68.9%) with stage II and 11 patients (24.4%) with stage III rectal cancer were included. Radiotherapy dosage, volume and schedule were as planned. Median time from diagnosis to start of radiotherapy was 26.36 days (24.26- 28.57; CI 95%). Median duration of radiotherapy was 6.00 days (5.56-6.44; CI 95%). Median time from start of radiotherapy to surgery was 15.67 days (14.47-16.87; CI 95%). Median time from completion of radiotherapy to surgery was 10.67 days (9.53-11.81; CI 95%). Most of the patients underwent low anterior resection [23 patients (51.2%)] and abdominoperineal resection [16 patients (35.6%)]. Correlation between clinical and pathologic staging was as expected. Twenty-nine patients (64.4%) of the 45 that were initially included started adjuvant chemotherapy. A statistically significant relationship between pathologic stage (grouped I-II vs. III) and the use of adjuvant chemotherapy was found (p=0.033; chi-square test). Radiotherapy- and chemotherapy-induced toxicity did not differ from that previously reported. With a median follow-up of 65.46 months, a total of 10 recurrences have been diagnosed, all of them in stage III patients. Overall survival rate at five years was 76% for the complete population included. CONCLUSION: Multidisciplinary treatment of resectable rectal cancer in a third-level hospital is feasible. Although efficacy results are comparable to those previously reported in the literature, further improvements in clinical staging as well as in adjuvant chemotherapy indication are desirable (AU)

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Transoral gastroplasty is safe, feasible, and induces significant weight loss in morbidly obese patients: results of the second human pilot study.

BACKGROUND AND STUDY AIMS: Bariatric surgical treatments have been proven to induce long-term weight loss in morbidly obese patients, but complications are relatively frequent. We recently reported a first human multicenter trial assessing the safety, feasibility, and weight loss results of the Transoral Gastroplasty (TOGA) system (Satiety Inc., Palo Alto, CA) at 6 months. Here we report the 6-month results of the second phase of the pilot trial with the TOGA system, with technical improvements to the device. PATIENTS AND METHODS: Patients met established criteria for bariatric surgery. The TOGA system, a set of transoral endoscopically guided staplers, was used to create a stapled restrictive pouch along the lesser curvature of the stomach. Follow-up was at 1 week and at 1, 3, and 6 months. At 3 months, re-treatment consisting in additional distal restrictions was allowed if necessary. RESULTS: Data were available for 11 patients in our center (7 female, mean age 44.2 years, mean body mass index 41.6). The procedure was completed safely in all patients. There were no serious adverse events. Mean excess weight loss was 19.2 %, 33.7 %, and 46.0 % at 1, 3, and 6 months, respectively. Average body mass index decreased from 41.6 before treatment to 33.1 at 6 months. Absolute mean weight loss was 9.9 kg, 17.5 kg, and 24.0 kg at 1, 3, and 6 months, respectively. A dramatic improvement in quality-of-life measures was observed in all patients. CONCLUSIONS: This second pilot trial confirmed the feasibility and safety of transoral gastroplasty. The early results and technical improvements reported in the present study are encouraging in terms of safety, early weight loss, and quality of life, and clearly allowed multicenter trials, which are planned to start soon.

Safety, feasibility and weight loss after transoral gastroplasty: First human multicenter study.

OBJECTIVE: To evaluate the safety and feasibility in human subjects of a new transoral restrictive procedure for the treatment of obesity. METHODS: The protocol was approved by the institutional review boards (IRBs) of both centers involved, and all patients gave informed consent. Patients met established inclusion criteria for bariatric surgery. The TOGa system (Satiety Inc., Palo Alto, CA), a set of transoral endoscopically guided staplers, was used to create a stapled restrictive pouch along the lesser curve of the stomach. Patients were hospitalized overnight for observation and underwent barium upper gastrointestinal (UGI) the next morning. Post procedure, all patients were placed on a liquid diet for 1 month and asked to begin an exercise program. Follow-up was carried out at 1 week and 1, 3, 4, 5, and 6 months. RESULTS: Twenty one patients were enrolled [17 female, age 43.7 (22-57) years, BMI 43.3 (35-53) kg/m(2)]. Device introduction was completed safely in all patients. There were no serious adverse events (AEs). The most commonly reported procedure or device related adverse events were vomiting, pain, nausea, and transient dysphagia. At 6 month endoscopy, all patients had persistent full or partial stapled sleeves. Gaps in the staple line were evident in 13 patients. Patients lost an average 17.6 pounds at 1 month, 24.5 pounds at three months, and 26.5 pounds at 6 months post-treatment [excess weight loss (EWL) of 16.2%, 22.6%, and 24.4%, respectively]. CONCLUSIONS: There is great interest in new procedures for morbid obesity that could offer lower morbidity than current options. Early experience with the TOGa procedure indicates that this transoral approach may be safe and feasible. Further experience with the device and technique should improve anatomic and functional outcomes in the future. Additional studies are underway.

[Strategy and critical analysis of bariatric surgery]. / Aspects stratégiques et analyse critique de la chirurgie bariatrique.

Bariatric surgery has considerably developed during the last 20 years in Belgium. The increase of prevalence of the morbid obesity and the development of multiple surgical procedures widened the spectrum of treatment. If a rigorous selection and a multidisciplinary approach of the patients are inescapable, the various decision-making algorithms plunge the practitioner into a certain confusion. The purpose of this paper is to clarify the advantages and the inconveniences of the different surgical treatments in light of the evolution of the principles and the objective results of the literature. Among the techniques proven and validated in the long run, one can mention the Silastic Ring Vertical Gastroplasty according to Mac Lean by minilaparotomy, the laparoscopic adjustable ring and the more recent gastric by pass. The evaluation of laparoscopic sleeve gastrectomy, and of duodenal switch is on course. The bilio-pancreatic by-pass according to Scopinaro remains strongly controversed. A meta-analysis of the literature confirms the success of the gastric bypass. Regarding to the long term follow-up, the adjustable gastric banding deceives. The sleeve gastrectomy should be analyzed in the long term. The preliminary results of a epidemiologic and financial study within a private hospital of Brussels reveals that the cost effective ratio is in favor the Silastic Ring Vertical Gastroplasty and the laparoscopic adjustable banding, as well in terms of public health support than the charge for the private insurance and the patient. The projection beyond 5 years reverses the tendency to plead in favor of the gastric by-pass. First with the hit-parade of comfort, food diversification, tolerance, gastro-esophageal reflux, and undoubtedly of the rate of recurrence, it supplants the others techniques for sweet eaters. The volume eaters can profit from a sleeve gastrectomy which undoubtedly supplants the Silastic Ring Vertical Gastroplasty responsible for late annular stenoses and reccurences.

Social protection sustainability, prolongation of working life and greater participation of women in the labour market.

One of the greatest problems of European societies is the financial sustainability of social protection systems in Europe. Together with Japan, Europe has the highest levels of ageing population in the world. This concern explains the reiterated insistence of the European Commission and the OECD regarding the reforms that governments should undertake. In this paper, reference is made to two of these reforms: prolonging of working life and a greater participation of women in the labour market.

Results of silastic ring vertical gastroplasty more than 6 years after surgery: analysis of a cohort of 214 patients.

BACKGROUND: Among the different techniques of surgical treatment for morbid obesity, silastic ring vertical gastroplasty (SRVG) is an alternative, effective and easily reproducible technique. The aim of this study is to evaluate a cohort of patients >6 years after SRVG for morbid obesity. METHODS: From 1991 to 1996, 273 consecutive patients were eligible for SRVG. The evaluation criteria included weight loss, evolution of co-morbidities, long-term morbidities, satisfaction of patients and quality of life. RESULTS: Among these 273 patients, 1 patient died in the postoperative period (0.4%). Postoperative morbidities occured in 27 patients (10%). The long-term follow-up involved 213 patients (78%). Late postoperative complications consisted of outlet stoma stenosis (14%), staple-line dehiscence (5.6%) and incisional hernia (8.5%). 23 patients (10%) needed a re-do operation. Co-morbidities drastically improved. BMI fell from 45.3 to 30.7. Failure of SRVG was statistically associated with male gender and super-obese patients. 69% of the patients were satisfied, and 73% would recommend this operation. CONCLUSION: SRVG is very effective in a selected group of morbidly obese patients.

La espiral del mobbing / The spiral mobbing

El acoso moral en el trabajo (Mobbing), lejos de constituirse como un problema puntual de las nuevas organizaciones se ha instaurado como una epidemia que afecta a miles de trabajadores. El conocimiento de su existencia, para los afectados y para los responsables de las organizaciones laborales contribuirá sin duda a su minimización como problema laboral, social y humano. La investigación sobre las bases de poder que se utilizan y los métodos que se aplican es uno de los aspectos cruciales en su afrontamiento. A nivel operativo, las organizaciones laborales y en su defecto los propios afectados pueden poner en marcha recursos que tiendan a erradicarlo (AU)

[The treatment of morbid obesity with gastroplasty]. / Traitement de l'obésité morbide par gastroplastie.

Morbid obesity is related to a severe decrease in life expectancy. No medical or dietary treatment offers an alternative to control hypertension, apnea syndrome, orthopedic diseases, ..., caused by overweight. With respect to a serious preoperative evaluation and a severe selection (psychologic, dietetic, ...) Silastic Ring Vertical Gastroplasty is considered in our experience (more than 300 cases) and in the literature as the gold standard for surgical treatment of obesity. The long term follow-up (24-66 months) of 100 consecutive operated patients shows a positive response on hypertension (96%), apnea syndrome (92%), diabetes (85%), gastroesophageal reflux (76%), orthopedic diseases (74%) and cardiorespiratory insufficiency (74%). Considering our experience in the medical and surgical management of patients operated in our department or referred from other centers for complications after different procedures, we actually propose SRVG as the treatment of choice for morbid obesity.

Bacterial mutagenic evaluation of Luxabendazole, a new broad spectrum anthelmintic, with the Salmonella typhimurium His- and the Escherichia coli Tryp- reversion tests.

Luxabendazole is a new benzimidazole carbamate chemotherapeutic agent, which has proved to be effective against adult and immature stages of the major gastrointestinal nematodes, trematodes and cestodes. The mutagenic properties of Luxabendazole were investigated in the in vitro Ames Salmonella and E. coli tests. The product was tested at concentrations of 0.5, 5, 50, 500, 1250 and 2500 micrograms/plate in the TA1535, TA1538, TA98 and TA100 strains of Salmonella typhimurium, and 0.5, 5, 50 and 500 micrograms/plate in the WP2, WP2uvrA- and its pKM 101-containing derivative CM891 (WP2 uvrA- pKM101) strains of Escherichia coli, with and without S9 microsomal activation (post-mitochondrial liver fraction from Wistar rats pretreated with Aroclor(R)). Positive and negative controls were included in each experiment. From the present study it can be concluded that Luxabendazole, over a dose range of 0.5-2500 micrograms/plate, is unlikely to present a mutagenic hazard, as demonstrated by the Ames test.

[Genotoxic study of commercial dyes with tartrazine base in S. typhimurium his- and E. coli trp-]. / Estudio genotóxico de colorantes comerciales con base Tartracina en S. typhimurium his- y E. coli trp-.

We study the genotoxic character of 21 food dyes samples with tartrazine in different trade-marks. Two homologated assays "in vitro" of reverse mutation in S. typhimurium and E. coli are used, with metabolic activation. There is no evidence of mutagenic character in any sample.