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"Isolation of non-conventional starches has increased in the last decade; chemical modification of these no conventional starches may produce starches with improved physicochemical and functional properties that are not available from commercial starches. Banana starch was acetylated and oxidized and the thermal, pasting and rheological characteristics were evaluated. The low carbonyl and carboxyl groups might be due to the starch source. The acetylated banana starch obtained had a low degree of substitution (0.04). The acetylated banana starch had lower temperature and enthalpy of gelatinization than oxidized and native banana starches, had higher peak viscosity in the viscoamylographic profile than its native counterpart. The oxidized starch produced the peak viscosity during the cooling step and the three starches had higher viscosity during the cooling step, showing a gel conformation. The native, acetylated and oxidized starches showed a non-Newtonian behavior of the shear-thinning type. The rotational test showed that oxidized banana starch had a firmer gel than acetylated starch, which agrees with the viscoamylographic results."

The feasibility of the ferritic alloy HT-9 as the main component of the first structural wall (FSW) of inertial confinement fusion (ICF) reactors, such as HIBALL-II or LIBRA, which use thin film li...

"El almidón de plátano fue acetilado a diferentes tiempos de reacción, se evaluaron el grado de sustitución, la velocidad de reacción, así como el patrón de difracción de rayos-X y las características morfológicas y térmicas. El grado se sustitución (GS) aumentó con el tiempo de reacción y consecuentemente también aumentó la eficiencia de la reacción. La constante de la velocidad de reacción fue mayor en el almidón de plátano (0.67 h-1) que en el de maíz (0.23 h-1). La espectroscopía de infrarrojo con transformada de Fourier confirmó la introducción de grupos acetilo en la molécula de almidón y la señal característica de este grupo (1226 cm-1) fue mayor a tiempos largos de reacción. La superficie del gránulo de almidón, observada por microscopía electrónica de barrido, mostró mayores cambios cuando el tiempo de reacción incrementó y fueron mínimos en el almidón de plátano. Este comportamiento coincide con los mayores picos de cristalinidad medidos por difracción de rayos X en el almidón de plátano y el patrón amorfo encontrado en el almidón de maíz acetilado. La temperatura (74.8 ºC para el almidón nativo de plátano y 71 ºC para su contraparte acetilada) y entalpía de gelatinización (12.89 J/g para el almidón nativo de plátano y 7.44 J/g para su contraparte acetilada) disminuyeron en los almidones acetilados y el efecto fue mayor a tiempos largos de reacción. Es posible determinar un cierto tiempo de reacción para obtener almidón de plátano acetilado con un GS específico, así como determinadas propiedades fisicoquímicas y funcionales."

Methods Stroke, dementia and epilepsy are the greater and most common disabling neurological diseases and were considered in this study. For each mentioned disease we will perform a Systematic reviews of all randomized clinical trials published in any language over the last 5 years with the aim of identifying and analyzing the outcome measures used in the evaluation of any kind of intervention. Fifteen Neurologists are filling out a single computerized form for each single trial assigned. The form has the following information: Characteristics of the trial with relevance on quality, Extent of variability in end points selected and their domains, Scales or techniques used to make the measurement, type of analysis applied and time of measurement, Presence of attrition bias in terms of fraction of patients reported by end points on the number enrolled in the study, Presence of outcome reporting bias in terms of end points declared and non-reported, end points not declared but reported, Source of funding. The valuation of patient and career needs and emotions will be performed with focus group discussions in a parallel section of the study.

Background Our Public Healthcare Service have developed some quality indicators (QI) based on the selection of drugs that support better evidence of efficiency in areas of prescribing where more deviations were detected in the past. Purpose To describe the strategies for improving the indicators, measuring compliance with them after three years and evaluating their financial impact on the public budget. Material and methods Retrospective observational study. The percentage of prescriptions of three QIs (omeprazole versus total PPIs, simvastatin versus total lipid-lowering drugs and ACE inhibitors versus total renin-angiotensin-aldosterone-system inhibitors) was evaluated before and after an educational program consisting of clinical sessions, meetings with the head of medical team (HMT) and Medical Director, periodic written reports for doctors and interviews with low-compliance-rate doctors. Prescription rates were measured in March 2011 and February 2014. Prescribing data and financial impact were obtained from the reimbursed drugs Program (Microstrategy), which enabled us to calculate the possible savings if the optimal level of prescriptions were to be reached. Results 24 clinical sessions were held in 2011, 17 in 2012 and 10 in 2013. Meetings with the HMT and Medical Director were biannual in 2011 and annual in 2012–13. 23 interviews were held, all in 2013. Reports were distributed in 100% of Units and possible periods. Omeprazole prescription was 69.3% at the beginning and increased to 85.4% three years later. Simvastatin prescribing also increased from 18.07% to 40.4%, and the percentage of ACE inhibitors rose from 28.44% to 52.82%. Regarding cost savings, in March 2011 drug expenditure in our Healthcare Area was €244, 717 more than with the theoretical optimum level of prescription, but in February 2014, this excess had reduced to just €44,803. Conclusion The strategies adopted were well received by the doctors, resulting in a considerable improvement of the indicators evaluated. This improvement now produces direct annual savings of €200,000 in the public budget in our Healthcare Area compared to three years ago. References and/or acknowledgements No conflict of interest.

Background Pharmacists prescribe and monitor, in consensus with Oncology, individualised Post-Chemotherapy antiemetic regimes for all patients in our Hospital. Purpose To evaluate the quality and the acceptance of the antiemetic treatment prescribed to breast cancer (BC) patients in the last five years. Material and methods Retrospective observational study of BC patients treated with standard chemotherapy who received antiemetic treatment between 2008 and 2013. Depending on the emetogenic potential (EP) of the chemotherapy scheme, the pharmacist assigned and explained to the patient/family the most suitable antiemetic regime as: Low EP: metoclopramide 10–20 mg tds as needed (PRN). Moderate EP (Kit-1): dexamethasone 4 mg tds 2 days, then 4 mg bid 2 days, then 4 mg od 2 days, and metoclopramide 10–20 mg tds PRN. High EP (Kit-3): Kit-1 plus granisetron 1 mg in the evening following chemotherapy. If the patient had no emesis on the previous cycle, the regime was reduced, but if nausea/vomiting were felt, the regime was stepped up. Patient/family was always involved in treatment decisions. Patient data, prescriptions and monitoring were collected from the Oncofarm application and Pharmacy Database and analysed using SPSS. Results 93 BC patients (all female) received a total of 400 chemotherapy cycles. 357 antiemetic prescriptions were dispensed, so 89.25% of the time a patient received chemotherapy, came to pharmacy for antiemetic drugs. 87.3% of anti-emesis patients started with Kit-3, and 12.9% with kit-1. Antiemetics were reduced in 63.4% of patients, 15.1% continued with the same regime and 21.5% required reinforcement: taking metoclopramide around-the-clock (16.1%), stepping up from kit-1 to kit-3 (3.2%) or adding lorazepam due to anticipatory nausea/vomiting (2.2%). Conclusion The large number of antiemetic prescriptions states the good acceptance from patients of the healthcare provided by the pharmacy. Progressive reduction of antiemetics in more than 60% of patients shows the good control and monitoring of nausea/vomiting with the antiemetic treatment prescribed. References and/or Acknowledgements No conflict of interest.

Background Pure red cell aplasia is a severe, non-regenerative form of anaemia, with selective erythroid aplasia of the bone marrow. Although there are congenital forms, most cases are adquired by toxic, radiation or drugs and 50% are idiopathic. Purpose Our objective is to describe the probable relationship between the occurrence of pure red cell aplasia and the treatment with adalimumab in a patient diagnosed with Crohn´s disease. Material and methods 22 years old woman who was admitted to hospital because of probably central origin anaemia secondary to adalimumab administration, over base severe iron deficiency. The variables analysed were: haemoglobin (g/dl), hematocrit (%), erythrocytes (×10 9 /l), leukocytes (×10 9 /l), platelets (×10 9 /l), serum iron (μg/dl), transferrin (mg/dl) and transferrin saturation index (%). Results The patient started treatment with adalimumab in November 2013 with an induction dose of 160 mg at week 0 and 80 mg at week 2, followed by 40 mg every other week. Baseline haemoglobin, erythrocytes and hematocrit were 11, 1 (norm. 12–15), 4, 18 (4–5) and 33, 8 (37–47), respectively. Concerning to iron study, baseline values of serum iron, transferrin and transferring saturation index were 22,4 (50–70), 217 (200–360) and 8, 13 (16–50), respectively. Platelets and leukocytes were in the normal range. After 5 months of treatment with adalimumab, the patient was admitted to hospital because of severe anaemia (haemoglobin = 4, 1, hematocrit = 14, 1 and erythtocytes = 2, 33), requiring stopping treatment and the administration of intravenous iron, 3 packed red blood cells and subcutaneous erythropoietin 40.000 once a week. After 5 weeks, the patient had haemoglobin values of 10.2 g/dl, showing a partial marrow recovery. Conclusion There have been rare cases of aplastic anaemia associated with the use of tumour necrosis factor antagonists, so that, although their relationship is unclear, patients with confirmed significant hematologic abnormalities should be considered to discontinue the treatment. Reference Kurvilla J, Leitch HA, Vickars LM, et al . Aplastic anemia following administration of a tumor necrosis factor-alfa-inhibitor. Eur J Haematol 2003;71:396–8 No conflict of interest.

Background Our Healthcare Area is implementing Medicines Reconciliation (MedRec) supported by The European Union Network for Patient Safety and Quality of Care. In a situation of limited human resources, computerised MedRec tools could help introduce medicines reconciliation. Purpose To describe a MedRec application that generates electronic alerts for general practitioners (GP) when patients are discharged from the Hospital with reconciliation errors (RE), and its impact in Primary Care after 3 months of implementation. Material and methods We have developed an application that can be integrated into the patient’s electronic medical records. The Application records the discrepancies (intentional/unintentional) of every MedRec Form made at admission or discharge and, at pharmacist demand, generates an electronic alert for the GP when a patient goes home with RE unsolved prior to hospital discharge (discrepancies between prescription at discharge and the active electronic prescriptions which allow regular pharmacy dispensing). In this retrospective observational study we measured REs and their severity at discharge, and the percentage of MedRec responded to by the GP after the alert was sent (considered correct if done before 5 days post-discharge). Data were analysed using SPSS. Results 46 reconciliation errors were found in a total of 63 patients (0.73 per patient) evaluated. Eight (17.4%) REs were considered highly relevant. All REs were found in 34 patients (54%), the other 29 patients being properly reconciled at discharge. From the 34 alerts generated for the corresponding GP, only 15 (44%) were acted upon and the patient’s medicines reconciled in less than 5 days. Five (62.5%) of the highly relevant REs were amended in less than 5 days post-discharge. Conclusion Less than a half of the alerts sent by the MedRec application were acted upon in a reasonable time. This means, although it can help in decreasing medicines errors in Primary Care, more time/training is needed for the GPs become more familiar with the tool. References and/or acknowledgements No conflict of interest.

Background In the absence of comparative studies of cetuximab vs. panitumumab in metastatic colorectal cancer (MCCR), we suggested performing an indirect comparison of the two drugs for this indication. Purpose To perform an adjusted indirect comparison of the two pivotal clinical trials of cetuximab and panitumumab, designed versus the best supportive care as a common comparator in patients with chemotherapy-refractory metastatic colorectal cancer. Material and methods On 5/04/2014 a literature search was performed in PubMed without finding indirect comparisons. The adjusted indirect comparison was performed with the results shown in subsequent updates of the pivotal clinical trials, in which subgroups of patients with K-RAS wild-type were analysed. We tested that the homogeneity of the population studied and the results of the treatment groups, were comparable with each other directly. Progression-free survival (PFS) was taken as the most clinically relevant variable available, as it allowed a proper comparison, although it was not the primary endpoint in either study. For our study we used the Bucher´s method, which combines the studies through analysis adjusted for the result of the control group. The Comparison Indirect Treatment (ITC) application, developed by the Canadian Agency for Drugs and Technologies in Heath (CADTH) was used. The margin of equivalence (the maximum difference considered clinically irrelevant) was defined. Results In the adjusted indirect comparison by the Bucher method, using the Wells calculator, an insignificant Hazard Ratio (HR) was obtained for cetuximab vs. panitumumab, relative to PFS. Therefore, we have no objective evidence that one drug is superior to another. The HR: 0.933 is very close to 1, and CI95% 0.624–1.396. The margin of equivalence established (0.67–1.49) is exceeded only at the lower limit, affecting a probability of 94.65% that the result is above 0.67, a result obtained by the Shakespeare calculator. Conclusion We consider that the two treatments might be considered as equivalent alternatives when referring to PFS in the third line. References and/or acknowledgements No conflict of interest.

Fibers made by a bioresorbable poly(epsilon-caprolactone)-block-poly(oxyethylene)-block-poly(epsilon-caprolactone) copolymer, having a number average molecular mass of about 200,000 Da and an average molar composition of 66% oxycaproyl units and 34% oxyethylene units, were melt-spun, with the aim at using them as suture threads. Their properties were investigated by the stress-strain test and by differential scanning calorimetry (DSC). The results obtained show that the properties of this material depend very strongly on the alignment of its macromolecules. In particular, the only partial alignment, obtainable by a relatively moderate drawing just after the extrusion, leads to values of elongation at break too high for use of the fibers as suture threads. The DSC analysis reveals interesting properties of the material, but also confirms their strong dependence on the extrusion procedure and on the mechanical treatment. In conclusion, the results of this preliminary study show that the spinning technique must be improved, and that further investigations are necessary to ascertain the possibility of using these poly(ester-ether-ester)s for the fabrication of suture threads.

Composite materials were prepared by mixing in different proportions of hydroxyapatite (HA) and poly(epsilon-caprolactone-oxyethylene-epsilon-caprolactone) block copolymer (PCL-POE-PCL) to produce a new resorbable material for biomedical applications. This material has proved to be very interesting for production of periodontal membranes. Mechanical properties are linearly proportional to the amount of HA introduced. Fourier transform infrared (FTIR) investigations have pointed out that HA is able to influence some close epsilon-caprolactone molecules to start its homopolymerization giving PCL with an end chain ionic bonding. HA grains are therefore surrounded by a film of PCL which grants close connection of HA grains within copolymeric matrix. This interface bond with PCL is, however, an interesting occurrence for preparations of HA/PCL composites.

Two chitosan-containing polyelectrolyte complexes, chitosan-poly(acrylic acid) and chitosan-poly(styrenesulphonate), were synthesized by polymerizing acrylic acid and sodium styrenesulphonate in the presence of chitosan and chitosan hydrochloride, respectively. The complexes were studied by optical microscopy and tested for cytotoxicity by the Neutral Red uptake, Kenacid Blue R-Binding and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assays. The optical microscopy confirmed the differences in crystallinity and structure already found for the two polycomplexes by other characterization techniques. The cytoxicity tests showed different influences on the cell activity by the extracts of the two polyelectrolyte complexes. Such results were discussed and correlated to the different structures of the two materials.

Biomembranes are frequently proposed as devices for "guided bone regeneration." Such membranes consist generally of a thin sheet of polymeric material, mostly textured from polymeric yarns or clots, which all have a diffuse very fine winding porosity. The cross-section size of the holes of such porosity is nanometric (diameter0.1 microm); thus these holes can be indicated as nanoholes. Whatever the method of production, the surface density of nanoholes (number per square centimeter) has to be as high as possible. It is important also that no variation of this density occurs. The fine dimension of these microholes allows the crossing of small molecules (O2, CO2, H2O, sugars, many nutritional organic compounds and even some simple proteins) but not other larger molecules and particulates, including cells of any kind. These biomembranes have, consequently, a semipermeable behavior, providing the functional role which is the interposition of a barrier for the cells, separating the bone from the surrounding soft tissues. The kinetic of proliferation of osteoblasts is lower than that of fibroblasts. Most membranes of this kind are not resorbable. The main problem for the resorbable ones is the speed of size increase of the holes during the time. Their diameter must not exceed a threshold value until the reconstruction of bone is complete, otherwise soft tissue cells will invade the growing bone tissue with formation of undesirable mixed tissue. The present paper deals with a resorbable membrane made with a composite polymer/ceramic. A poly(epsilon-caprolactone)-block-poly(oxyethylene)-block-poly(epsilon-caprolactone) copolymer is the polymeric matrix which contains dispersed ceramic hydroxyapatite microgranules, a stiff filling additive. The main possible use is that of periodontal membranes. The copolymer, obtained by thermal polymerization of epsilon-caprolactone onto poly(ethylene-glycol), presents good biological tolerance, is resorbable under physiological conditions and can promote cell growth. Histological tests, performed 6 months after implantation, showed that the polymeric matrix is almost totally resorbed. New-formed bone colonizes even the innermost parts of the membrane, with bone trabeculae closely surrounding the hydroxyapatite granules.

The 5-fluorouracil release by biodegradable epsilon-caprolactone and L-lactide copoly(ester-ether-ester)s was tested. The drug-copolymer mixture was formed by fusion in thin sheets, which were dipped in Dulbecco's PBS for time intervals ranging from one hour to two months. Each experiment shows a fast initial release, which subsequently slows down and stops at a limiting value, depending on the copolymer composition. This behavior was attributed to an extraction of the drug present on the sheet surface, due only to its shape, and to hydrogen bonds between the drug and the copolymers. The results obtained lead to a possibility of using such copolymers as "time-delayed" drug-releasing systems, when formed in specimens with smaller surface-to-volume ratio, which could minimize the fast initial extraction.

Psychiatric issues present a challenge in the treatment of patients with multidrug-resistant tuberculosis (MDR-TB). Both baseline psychiatric disorders and development of psychiatric complications related to anti-tuberculosis drugs and psychosocial factors require aggressive management.A community-based non-governmental health organization in Lima, Peru.To review the literature for psychiatric complications associated with anti-tuberculosis medications, to describe the incidence and prevalence of depression, anxiety and psychosis among individuals receiving MDR-TB therapy, and to detail the management approach used in this cohort.A retrospective case series was performed among the first 75 patients to receive individualized MDR-TB therapy in Lima, Peru, between 1996 and 1999.Baseline depression and baseline anxiety were observed in respectively 52.2% and 8.7% of this cohort. Most individuals with baseline depression experienced improvement of depressive symptoms during the course of TB therapy. The incidence of depression, anxiety and psychosis during MDR-TB treatment was 13.3%, 12.0% and 12.0%, respectively. While the majority of individuals with depression, anxiety and psychosis required psychiatric pharmacotherapy, cycloserine was successfully continued in all but one case.Psychiatric comorbidities are not a contra-indication to MDR-TB therapy. Management of psychiatric complications is possible without compromising anti-tuberculosis treatment.

The hydroxyls present on the surface of hydroxyapatite (HA) granules, annealed at 700 composite function, 900 composite function and 1,100 composite function C, are able to initiate the polymerization of epsilon-caprolactone (CL), not only at 185 composite function C under vacuum, but also at room temperature in open system. A polymer layer ionically linked to the substrate is formed on HA surface, enhancing the compatibility between the organic phase and the inorganic one in composite biomaterials. We studied the characteristics of the polymer, produced by the reaction carried out at room temperature in open system, as well as the percentages of the poly(epsilon-caprolactone) (PCL) ionically bonded to the HA structure and of the "free" one. Both percentages appear very dependent on the annealing temperature; in particular, HA annealed for 1 h at 1,100 composite function C is the most efficient initiator of the reaction leading to ionically bonded PCL. The percentages of "free" polymer are much higher than at 185 composite function C under vacuum. Its formation is attributed to the role of water in opening the CL rings, and to the presence of CO(3) (2-) and HPO(4) (2-) ions in the HA annealed at lower temperatures. The presence of water appears to be the limiting factor for the production of PCL not bonded to the HA structure.

Since 2000, the directly observed treatment, short-course (DOTS) strategy has been expanded in several countries to include treatment of multidrug-resistant tuberculosis (MDR-TB). This strategy is known as DOTS-Plus. Tuberculosis is a common cause of morbidity and mortality for children throughout the developing world. Children may also be infected with MDR-TB, yet most developing countries do not specifically address pediatric MDR-TB.To present the intermediate outcomes of the first 16 children enrolled in the Peruvian DOTS-Plus program and to demonstrate the tolerability of second-line anti-tuberculosis drugs.Three children completed therapy and are cured, one child had bacteriologic and clinical failure after 12 months of therapy and died of respiratory insufficiency, and 12 have intermediate outcomes demonstrating favorable clinical, bacteriologic, and radiographic evidence of improvement after 9-19 months of therapy.Of the 16 pediatric DOTS-Plus patients, 15 have tolerated therapy well and have had favorable clinical evolution. However, the diagnosis of pediatric MDR-TB is often extremely delayed due to reliance on the adult case definition and should be changed to prevent progressive, chronic illness in such children. Programmatic changes could facilitate earlier diagnosis and treatment of pediatric MDR-TB in Peru and in other DOTS-Plus programs.

A community-based treatment program for multidrug-resistant tuberculosis (MDR-TB) in Lima, Peru.To describe the activities carried out by the nurses working with the program.A qualitative study using a variety of ethnographic methods, including participant observation, focus groups, and key informant interviews over a 5-year period.Nurses were responsible for carrying out a wide variety of activities within the program. These included patient-focused activities such as identifying patients, evaluating patients prior to starting and during therapy, and managing emergencies; educational activities for both patients and health professionals managing MDR-TB; and coordination activities, including over-seeing health workers and communicating between team members.Nurses play a key role in the community-based management of MDR-TB.

Background Acne inversa (AI), also known as suppurative hidradenitis (HS), is a chronic, inflammatory, recurrent disease that is difficult to manage with the usual standard treatment, especially in the advanced stage of the disease. So the use of factors modulating the inflammatory response such as adalimumab may constitute a new therapeutic option. Purpose To evaluate the efficacy and safety of adalimumab in the treatment of severe AI. Materials and methods Retrospective cross-sectional study of patients diagnosed with AI (Hurley grade III) and adalimumab subcutaneous until August 2013. In all cases, informed consent was obtained (off-label indication). The data were obtained from the clinical history and computerised outpatient dispensing program. The efficacy of adalimumab was defined as clinical improvement in the affected regions, nodules and/or fistulas compared to the usual standard treatment (oral antibiotics, corticosteroids, antiandrogens and/or retinoids). Results Six patients were included, 2 men and 4 women, with a mean age of 28.8 ± 8.6 years (range: 17–39). The mean treatment duration was 4.8 ± 2.7 months (range: 1–9). In men, the affected regions were the genitals and the groin, while in women they were the armpits and groin. In one case, the affected area was not reflected in the medical history. 3 patients were active smokers. All patients had been treated previously with oral antibiotics, combined or not with antiandrogens, corticosteroids and/or isotretinoin and none had previously received a biological therapy. Only in one case there was a positive family history of the disease. 4 patients received loading doses of 160 and 80 mg administered subcutaneously at week 0 and 1, respectively (without interval) and 2 patients received loading dose of 80 mg at week 0. The maintenance regimen was 40 mg weekly except in 2 cases it was every other week, one because of severe headaches. All patients reported improvement with decreased drainage from all affected sites, remaining stable during the follow-up period. No significant adverse effects were reported. Conclusions Adalimumab may represent a new alternative in the management of severe AI with an acceptable safety profile, despite being administered at high doses during the induction phase and without a weekly break; the long-term benefit/risk of adalimumab is unknown. No conflict of interest.

Background An association between sitagliptin and myopathy is exceptional, although four cases of rhabdomyolysis caused by a statin-sitagliptin interaction have been already reported, one of them with atorvastatin. Purpose To present a case of rhabdomyolysis with hypomagnesemia and acute kidney failure possibly caused by an interaction between sitagliptin and atorvastatin. Materials and methods Description of the clinical picture, physical examination and laboratory data: serum electrolytes, kidney function blood test, creatine phosphokinase (CPK) and lactic dehydrogenase (LDH). Use of the Drug Interaction Probability Scale (DIPS) to establish a possible interaction between the two drugs. Results An 80-year-old man with hypertension, diabetes treated with metformin, dyslipidaemia, myocardial infarction and recent stroke, admitted because of asthenia, confusional syndrome, myalgia, muscle cramps and fasciculations. Chronic medicines included furosemide 40 mg od, manidipine 10 mg od, famotidine 20 mg od and zolpidem 10 mg nocte. The patient became unwell after atorvastatin was increased from 40 to 80 mg/day because of the stroke, and after adding sitagliptin to metformin because poor glycaemic control. Laboratory data: urea 49.3 mg/dL; creatinine 1.45 mg/dL; sodium 145.2 mg/dL; potassium 3.3 mg/dL; calcium 4.9 mg/dL; P 5.1 mg/dL; magnesium 0.9 mg/dL; CPK 1253 IU/L; LDH 352 mg/dL; albumin 2.6 mg/dL; uric acid 9.2 mg/dL; D-vitamin 43.0 ng/mL. Calcium gluconate 10% (IV) and oral magnesium lactate (60 mg/day) were prescribed. When blood calcium levels reached 8–9 mg/dL, treatment was switched to oral. Clinical and analytical improvements were observed seven days after sitagliptin and atorvastatin were interrupted. Atorvastatin (40 mg/day) was reintroduced later. Calcium, magnesium, uric acid, CPK and LDH went back to normality. By contrast, kidney function has not completely recovered. DIPS indicated a possible interaction (score of 4) between sitagliptin and atorvastatin. Conclusions There was a possible interaction between sitagliptin and atorvastatin. The atorvastatin dose had been increased from 40 to 80 mg, so it cannot be assumed that the clinical profile was entirely caused by the introduction of sitagliptin. Furthers studies are needed about the effect of sitagliptin on the cytochrome P4503A4 system. Meanwhile, this interaction should be taken into account by prescribers and pharmacists. No conflict of interest.

Background In order to bring prescriptions for the use of direct-acting antiviral agents (DAAs) for the treatment of HCV genotype 1 infection in mono and co-infected patients in line with the recommendations of the Spanish Health System under the current economic conditions, a local committee formed by an Infectious Disease specialist, a Gastroenterologist and a Hospital Pharmacist was created in our Health Care Area. Purpose To evaluate the economic impact of prioritising treatments with DAAs decided by a local committee in a Health Care Area over 18 months. Materials and methods Observational, retrospective study from April 12 to September 13. Viral genotype was ascertained, as well as liver stiffness by ultrasound-based transient elastography (FibroScan) and IL-28 polymorphism. Patients were classified based on previous treatment with peginterferon-ribavirin (treatment-naive, relapser, partial-responder, non-responder or with unknown previous response). By agreement between the Medical Director, Pharmacy, Gastroenterology and Infectious Disease Services, patients considered eligible for treatment with DAAs were those with stage F3-F4 fibrosis and those relapsers whose liver stiffness was >8.5 kpa. Medical records and laboratory data of all patients with a request for treatment with DAAs were reviewed as well as the decision taken by the Commission (accepted/denied). The cost with triple therapy in HCV genotype 1 was estimated to be 40,000 € per patient (treatment and supportive treatment). Data was analysed using SPSS. Results 56 treatment requests were finally evaluated. Depending on previous treatment, patients were treatment-naive (46.42%), relapsers (37.5%), partial-responders (10.71%) and non-responders (5.35%). Classed by stage of fibrosis, they were F0-F2 (25%), F3-F4 (57.14%), and 17.85% had no recent fibrosis test (neither FibroScan nor biopsy). 93.9% of accepted prescriptions corresponded to F3-F4 patients and the remaining 6.1% were two exceptions to the current HCV therapy recommendations of the Spanish Health System (one F2 treatment-naive woman with childbearing intentions and one F2 treatment-naive man with special working conditions). 23 (41.1%) patients were considered not eligible for triple therapy with DAAs. That resulted in a cost saving of 880,000 € (one of them had no indication for treatment (F0-F1), so was not included). Conclusions The creation of a local committee with powers to prioritise triple therapy with DAAs to those patients with more advanced liver disease and to defer such treatment of those in the early stages (hoping for new, better and safer drugs) has already generated important cost savings in our Health Care Area. No conflict of interest.

Background According to current clinical guidelines developed from evidence-based medicine, heart failure with ventricular dysfunction needs to be treated with the combination of an ACE inhibitor and a beta blocker. An aldosterone antagonist should be added in the more advanced stages of heart failure or recent myocardial infarction. Purpose To review the treatment of patients diagnosed with heart failure in order to evaluate whether they were properly treated according to current clinical guidelines. Materials and methods In 2012 we conducted a retrospective review of the medical records of all patients admitted to the Internal Medicine Service of a second level hospital with a discharge diagnosis (principal diagnosis or comorbidity) of heart failure. 100 paper medical charts were randomly selected from a total of 521 found and clinical, laboratory and echocardiographic data and patient’s medicines at discharge were collected and analysed using the SPSS statistical package. Results With regard to cardiovascular drugs, discharge treatment included diuretics (85%), ACE inhibitors (42%), statins (39%), digoxin (35%), ARBs (30%), calcium antagonists (24%) and beta blockers (24%). Unfortunately no distinction was made in the data collection between different types of diuretics, so analysis of aldosterone antagonist therapy was missed. 65% of the patients had heart failure with systolic dysfunction, of which 68% were female and had a mean age of 74.6 years. The primary reasons for admission were: respiratory infection (31%), cardiac arrhythmia (28%) and cardiac ischemia (20%). Comorbidities associated with heart failure were hypertension (70%), diabetes mellitus (52%), atrial fibrillation (33%), COPD (15%) and chronic renal failure (10%). 28% of patients didn’t received any drug blocking the renin angiotensin system, and an even higher percentage, 76%, no beta blocker, although both groups of drugs are well known for improving survival. Of those patients prescribed an ARB antagonist or an ACE inhibitor, a higher percentage of patients received an ARB inhibitor (42%) than was felt justified. Conclusions The data indicate that, according to current recommendations, a significant percentage of patients are undertreated. The high percentage of patients prescribed diuretics suggests the focus is on symptom relief, rather than on prognosis. These findings are consistent with the literature and indicate that there are legitimate reasons for undertreatment by general physicians, such as the concern of adding a hypotensive drug or a potentially nephrotoxic drug in elderly patients with multiple significant comorbidities. A specialist heart failure team in our area would benefit patients by minimising unnecessary drugs (including diuretics) and initiating and uptitrating ACE inhibitors and beta blockers in these patients. No conflict of interest.

Background Dapsone is an antileprotic whose mechanism of action for linear IgA dermatosis is not yet known. Purpose To evaluate the efficacy and safety of dapsone in the treatment of linear IgA dermatosis in a paediatric patient. Materials and methods Review of the clinical history, consultation of the outpatients dispensing software (Dipex) at the Pharmacy Unit, as well as the electronic laboratory records (Izasa). Drug efficacy was assessed by the clinical evolution of dermatological manifestations, while safety was evaluated by monitoring liver function, haemoglobin (Hb) and adverse reactions listed in the drug’s SPC. Results The study subject was a 2 year-old patient who presented disseminated bullous eruptions over the perigenital area, accompanied by intense itching. Initial treatment consisted in high-potency corticosteroid and topical fusidic acid, in addition to recommending a gluten free diet for suspected diagnosis of linear IgA dermatosis, later confirmed by a direct immunofluorescence study. After only slight improvement of the lesions, it was decided to start treatment with dapsone 25 mg/day, following the SPC recommendations not to exceed 2 mg/kg/day. A dramatic response was observed, together with regular values in blood tests. The only adverse effect experienced was nausea. Due to a decrease in Hb values, after 4 months of treatment, the pattern of administration was spaced to alternate days, maintaining good control of the disease, although occasional diarrhoea was reported. Liver and hematologic functions remained within normal limits in the regular checks. Because of flare-ups, the dose was eventually increased to 25 mg/day, then decreased again after remission of the episode to 25 mg every third day, a pattern that continues at present, 4 years after starting treatment. Conclusions Dapsone achieves good control of linear IgA dermatosis in our paediatric patient, but continual revisions of the dose are required. Although gastrointestinal adverse reactions and occasional decreases in Hb levels have been observed, it can be concluded that the drug’s long-term safety profile is acceptable in this case. Further well designed studies are required in order to generalise the results obtained. No conflict of interest.

Background Polymedicated patients are susceptible to medicines errors. Ensuring good compliance through medicines reconcilliation and follow-up after hospital discharge may be useful in improving control of chronic diseases and patient safety. Purpose To assess the degree of compliance with chronic treatment prescribed at discharge and to determine the degree of satisfaction of the monitoring and support of polymedicated patients at home. Materials and methods Interventional study conducted by a multidisciplinary team consisting of the Pharmacy Service, Inpatient Nursing Unit and doctors from Internal Medicine. We included all patients over 60 years old on active treatment with 6 or more drugs, and stable home treatment, who were admitted to the Internal Medicine Department from November 2012 to July 2013. The intervention consisted of reconciliation of home treatment on admission and at discharge, which provided oral information and written instructions to follow at home. Three weeks after discharge, the pharmacist made a home visit where the changes to the discharge medicines were checked and the degree of compliance with the treatment was verified. The patient was considered to have good adherence when the consumption of the prescribed tablets was between 80 and 110%. One month after the visit, a telephone survey was conducted by an external professional of the project, in which the patient, family and/or caregiver could assess the information provided, professionalism and overall satisfaction with the service. Results We included a total of 74 patients, 62.2% (46) of whom were women, with a mean age of 77.8 ± 6.8; 27% (36) were functionally dependent patients (moderate, severe or complete) according to the Barthel index. 47% were taking between 10 and 14 drugs at home. After interviewing the patients at home, the recorded degree of compliance was 94.6% (70) of the studied population. 70.3% (52) of those visited completed the satisfaction survey, of whom 65.4% (34) were family/caregiver and 34.6% (18) patients. 86.5% (45) of the patients appreciated the professionalism of the team. 78.8% (41) considered that the information provided had been helpful. Finally, 94.2% (49) of the patients expressed overall satisfaction with the service. Conclusions The reconciliation process at discharge, with individual attention and subsequent monitoring at the patient’s home could ensure appropriate compliance with chronic treatment, with a consequent reduction in medicines errors and adverse effects. No conflict of interest.

Background The length of treatment with triple therapy against hepatitis C virus genotype 1 (HCV-1), which comprises telaprevir, ribavirin and peginterferon α-2b, is variable, depending on the patient to be treated. Purpose To evaluate the use and effectiveness of telaprevir in HCV-1 patients according to the SPC guidelines. Materials and methods Retrospective observational study of HCV-1 mono-infected patients who started treatment with telaprevir, ribavirin and peginterferon α -2b. The follow-up period was 48 weeks. The variables analysed were: type of patient (treatment-naive, relapsed, partial responder and non-responder), viral load (VL) at baseline, at 4, 12, 24, 36 and 48 weeks (IU/ml) and duration of treatment. For treatment-naive and relapsed patients in which VL was undetectable at week 4 and 12, the treatment lasted 24 weeks, extending up to 48 weeks in patients with detectable VL. In the case of partial responders or non-responders, it is always 48 weeks. Furthermore, criteria for considering discontinuation were: VL >1000 (IU/ml) at weeks 4 or 12, and detectable VL at weeks 24 or 36, since it was unlikely that these patients would obtain a sustained viral response. Results A total of 17 patients were included. Of the treatment-naive and relapsed patients (14), the treatment of 2 of them did not follow the SPC. Although both had undetectable VL at 4 and 12 weeks the treatment continued for 48 weeks. Among partial responder and non-responder patients (3), 1 did not follow SPC recommendations; treatment was suspended after 24 weeks, but VL was detectable again at week 48. Premature suspension in this case was not due to toxicity reasons. Viral load remained undetectable at week 48 in 14 of the remaining patients. Conclusions The treatment in our study did not follow SPC recommendations in 18% (3/17) of patients. Triple therapy was not effective in 1 of 3 patients who stopped at week 24 (shorter than recommended). We advise establishing a cutoff point at week 24, and evaluating the patient type (treatment-naive/relapsed or partial responder/non-responder) before deciding to suspend treatment early, as well as determining VL at weeks 4 and 12 for correct adjustment of treatment duration. No conflict of interest.

Background The Andalusian Public Health Care Service have developed some indicators based on the selection of drugs for which there is better evidence of efficiency within several therapeutic groups, in areas of prescribing in which more deviations were detected in the past. Purpose To improve the prescribing in a rheumatology team, in terms of efficiency, through the implementation of three quality prescribing indicators, and to measure its degree of compliance after completion of an educational program. Materials and methods Retrospective observational study that measures the percentage of prescriptions meeting three quality indicators before and after an educational program consisting of clinical sessions, meetings with the head of the rheumatology team and/or meetings with medical direction and management direction. Doctors also had information on their results every three months. The three indicators measured were: percentage of generic-name prescriptions versus total prescriptions, percentage of first-line NSAIDs (naproxen, diclofenac and ibuprofen) prescribed versus total NSAIDs and percentage of alendronate, Calcium and Vitamin D versus total of drugs approved for fracture prevention. The prescription rates were measured in October 2012, before the beginning of the educational program, and in August 2013, when it had ended. Prescribing data were obtained from the pharmacy’s computerised reimbursed drugs records (Microstrategy) of all physicians who belonged to the rheumatology team for at least one month during the time studied. Results The initial team of six doctors was monitored. At the end of the study no one had left and no new doctors were incorporated. Three clinical sessions were given by the pharmacist in charge, plus two meetings between him and the chief doctor, and another two between the pharmacist, Chief Doctor and Medical Director. Generic prescription was 72.02% at the beginning and had increased to 83.77% ten months later. First-line NSAIDs prescribing also increased from 18.23% to 46.06%, and the percentage of first-line drugs for fracture prevention (Ca, vit. D and alendronate) rose from 27.05% to 42.50% at the end of the study. Conclusions Prescription of generic-name drugs, first-choice NSAIDs and first-line drugs for fracture prevention improved in a Rheumatology Unit due to an educational prescribing course based on clinical evidence guidelines. The initiative was popular with the doctors, and the commitment of the Medical Director was important to obtain these results. No conflict of interest.

We present a male patient with a facial haemangioma extending from the lower left lid to the malar region and the upper left lip. The patient also presents a 1 cm round cutaneous notch on the upper third of the sternum. There are not other physical anomalies. The characteristics of the clinical picture suggest the diagnosis of sternal cleft-haemangiomas malformative spectrum (OMIM 140850).

We report two patients with trisomy 21 whose karyotypes revealed unusual translocations. In the first case there was a tandem translocation with two chromosomes 21 attached to the long arm of chromosome 10 (45,XX + tan(10:21;21). In the second case there was an inverted tandem translocation between two chromosomes 21 attached through their long arms (46,XY + dic(21q:21q). The clinical picture in both patients was not different from the usually found in trisomy 21. Since the parent's karyotypes were normal in both cases, it is assumed that both translocations arose "de novo". The need for karyotyping all cases of Down syndrome is emphasized.

Achondroplasia and trisomy 21 are, within their respective categories, conditions the most frequent genetic diseases found in newborns. The simultaneous presence of both conditions in the same patient, has been however, reported only once in the world literature. In this paper we present a patient affected by both entities (Achondroplasia and Trisomy 21). The clinical findings and the reasons for the rare reported frequency of these cases are discussed.

Marmoset monkeys are an useful model to biological human experiments and their development in captivity has been carried out in different environment and feeding conditions. This work presents the development of Callithrix jacchus jacchus and Callithrix jacchus penicillata in captivity at the vivarium of the Centro de Biologia da Reprodução. Couples of marmosets, obtained with the help of the Forest Institute, were kept in an environment where the temperature was around 22-24 degrees C, with 10 hs of light per day and fed on a diet of dog chow pellets, bananas, eggs, carrots, Farinha Láctea (Nestlé) and milk. Comparing the number of newborns/delivery, interbirth delivery, and some other indicators, it was concluded that the development of Callithrix jacchus jacchus is compatible with other colonies cited in the literature. The development of Callithrix jacchus penicillata, on which no report has been found, is similar to that of Callithrix jacchus jacchus.

Microtia is a congenital malformation characterized by total or partial absence of the whole auricle or any of its components, varying from a small auricle to the total absence (anotia). There may be associated atresia of the external auditory meatus. The frequency varies in different parts of the world between 0.4 and 5.5/10,000 newborns. In this paper we report the clinical and epidemiological characterization of this congenital malformation in a sample of 97.759 neonates born at the Ruíz y Páez Hospital in Ciudad Bolivar, Venezuela, between April 1978 and December 1994. A total of 38 patients with microtia were identified. The global frequency was 3.8 per 10,000/newborns. In 47.4% of the patients microtia was an isolated malformation and in 52.6% was associated to other malformations. Sixty three percent of the affected were males. The unilateral form was present in 81.5% of the cases, more frequently on the right side. The annual frequency of the defect was stable over the studied years. The clinical classification of the cases with associated malformations allowed us to establish that 18.4% of the cases correspond to developmental fields defects, associated to preauricular dimples and/or tags, 7.8% were cases of the facio-auriculo-vertebral spectrum and in 15.7% the microtia was part of a monogenic or chromosomal syndrome. In 10.5% it was not possible to define any etiological or pathogenic mechanism. The frequency obtained in this study for microtia shows intermediate values when compared with others reports from Latin America.

We report two brothers from non-consanguineous parents who share a particular constellation of clinical and radiographic findings, including macrocephaly, mental retardation and seizures as well as megalencephaly, cavum septum pellucidum and persistence of cavum vergae. The similar characteristics of these two brothers suggest a hereditary syndrome.

A 2 years and 9 months old female patient, with the diagnosis of Weaver syndrome is reported. The proband presents persistent pre and post-natal overgrowth, asynchronic advanced bone age, particular facies, (macrocephaly, ocular hypertelorism, micrognathia, large ears), bilateral widening of the distal femoral metaphysis, bilateral tibia vara, prominent fetal fingerpads, clinodactyly, development delay, low pitched and hoarse cry, nonspecific cortical atrophy, dilation of the ventricles and vermix hypoplasia. The differential diagnosis with other overgrowth syndromes is discussed. The possibility of uniparental disomy and genetic imprinting as the basic genetic defect in the Weaver syndrome is suggested. The patient reported here appears to be the first case in the Venezuelan literature.

Background The addition of telaprevir to standard treatment considerably improves response rates and allows the duration of treatment to be reduced in a significant number of patients. Purpose To assess the efficacy and safety of telaprevir in combination with peginterferon alfa-2b and ribavirin (RBV) in patients with hepatitis C virus genotype 1 (HCV). Materials and Methods Retrospective observational study of patients mono-infected with HCV genotype 1, treatment-naive and pretreated, who started treatment with telaprevir. The follow-up period was 24 weeks. Relapsed patients were defined as those with undetectable viral load at the end of treatment but detectable at 24 weeks’ follow-up, partial responders as ≥2log10 decline in viral RNA at week 12 but without undetectable viral load at week 24 and null responders as Results We included 16 patients (81.3% men and 18.8% women). 15 patients presented undetectable viral load at weeks 4 and 12, reducing the duration of treatment to 24 weeks. RBV dose was reduced in 6 patients and 2 patients started with a dose of 600 mg, in both cases without compromising treatment success. 7 patients had anaemia, of whom 2 required transfusions and erythropoietin. 12 cases had skin toxicity (8 mild, 3 moderate and 1 severe with subsequent interruption of treatment at week 4). Conclusions The data confirm those reported in the ILLUMINATE study, with high rates of rapid virological response and reduction of treatment from 48 to 24 weeks, but with a higher rate of skin toxicity although mostly mild to moderate. No conflict of interest.

Findings are presented of a European study (conducted in the UK, Italy, Spain and The Netherlands) of family relationships and the social and emotional development of children in families created as a result of the two most widely used reproductive technologies, in-vitro fertilization (IVF) and donor insemination (DI), in comparison with control groups of families with naturally conceived child and adoptive families. Mothers of children conceived by assisted reproduction expressed greater warmth towards their child, were more emotionally involved with their child, interacted more with their child and reported less stress associated with parenting than mothers who conceived their child naturally. Similarly, assisted reproduction fathers were found to interact more with their child and to contribute more to parenting than fathers with a naturally conceived child. With respect to the children themselves, no group differences were found for either the presence of psychological disorder or for children's perceptions of the quality of family relationships. The findings relating to the quality of parenting and the socio-emotional development of the children were similar in each of the four countries studied.

Cytochemical and immunocytochemical approaches have been applied to the study of the surface of articular cartilage in humans, bovine and rats. Specimens were fixed in situ or soon after bioptic sampling with chemicals able to preserve and visualize proteins (glutaraldehyde, tannic acid), lipids (osmium tetroxide, malachite green, uranyl acetate) and proteoglycans (toluidine blue O, cuprolinic blue, cetyl pyridinium chloride). Mixtures of reagents were also used. Oriented serial thin sections were observed as such or after treatment with chemicals (chloroform-methanol, Triton X 100) or enzymes (chondroitinases, hyaluronidases, trypsin). Hyaluronan was detected by the use of glial-hyaluronate-binding-protein and antibodies against it. High concentration of osmium tetroxide or fixatives containing markers for lipid or for proteoglycans revealed that the surface of the articular cartilage, in all animal species examined, was covered by mono-multilayered discontinuous three-laminar sheets, which could be partly removed by chloroform-methanol and Triton X 100, were sensitive to hyaluronidase, chondroitinase and trypsin, and were immunopositive for hyaluronan. Each three-laminar sheet was 12-14 nm thick, was always separated from the cartilage itself and could be easily displaced. It is proposed that the surface of normal articular cartilage is covered by a discontinuous mono/multilayered pseudo-membrane, that can be better preserved by fixatives injected into the joint cavity and seems to consist of phospholipids, glycosaminoglycans and proteins. This membrane-like structure might have a protecting role in preventing direct contacts between the articular cartilage and toxic agents present in the synovial fluid and/or exert a lubricating effect within the articular joint.

Gastric volvulus in children might be observed both as an acute form, characterized by gastric necrosis with sudden perforation and patient's death and as an idiopathic or chronic form with a less severe insurgence that causes epigastric pain, vomit and gastric distension. The latter could resolve spontaneously but recurs frequently. The acute form rises in newborns and toddlers and is often associated with a diaphragmatic defect; the idiopathic forms are correlated on the opposite to a fixation deficit of the stomach which is held in place by the gastro-colic, gastro-hepatic, gastro phrenic and gastro-splenic ligaments. Since a diagnostic mistake could cause the patient's death gastric volvulus must be carefully considered as a possible cause of acute epigastric pain with vomit. In the two forms surgical therapy is mandatory for the simultaneous correction of both the anatomical defects of gastric fixation and malposition and the diaphragmatic ones. The case presented is an example of an acute gastric volvulus in a 2-year-old male child affected by a diaphragmatic defect The peculiar aspect of this case consists in the age of arousal being more usual in an earlier age An appropriate surgical treatment has permitted the patient's recovery.

We tested the hypothesis that the level of the DNA repair protein O6-alkylguanine-DNA alkyltransferase in brain tumors was correlated with resistance to carmustine (BCNU) chemotherapy. Alkyltransferase levels in individual cells in sections from 167 primary brain tumors treated with BCNU were quantitated with an immunofluorescence assay using monoclonal antibodies against human alkyltransferase. Patients with high levels of alkyltransferase had shorter time to treatment failure (P = 0.05) and death (P = 0.004) and a death rate 1.7 times greater than patients with low alkyltransferase levels. Furthermore, the size of the subpopulation of cells with high levels of alkyltransferase was correlated directly with drug resistance. For all tumors the variables most closely correlated with survival, in order of importance, were age, tumor grade, and alkyltransferase levels. For glioblastoma multiforme, survival was more strongly correlated with alkyltransferase levels than with age. These results should encourage prospective studies to evaluate alkyltransferase levels as a method, for identifying brain tumor patients with the best likelihood of response to BCNU chemotherapy.

The radical polymerization of acrylic acid and sodium 4-styrenesulfonate in the presence of chitosan as a template gives insoluble products, identified as the polyelectrolyte complexes chitosan-poly(acrylic acid) and chitosan-poly(4-styrenesulfonate). Kinetic results do not permit to propose any mechanism in the first case, while suggest a “pick-up” one in the second. The polyelectrolyte complexes have been characterized by FT-IR spectroscopy, X-ray diffractometry, optical and scanning electron microscopies, differential scanning calorimetry and thermogravimetric analysis. The results obtained indicate an ordered structure for the first complex, while the second one appears similar to that obtained by reacting the parent polymers. Therefore, the template polymerization technique appears advantageous only for the synthesis of the chitosan-poly(acrylic acid) complex. The thermal analysis shows that the complexes undergo two successive modifications on heating. FT-IR analysis demonstrates that the first process is an esterification between the hydroxyls of chitosan and the acidic groups of both daughter polymers; the second one appears to be an amidation of the chitosan ammonium groups only with the sulfonate groups.

Electrocardiography was applied to analyze cardiac function of four teleost species (Piaractus mesopotamicus, Hoplias malabaricus, Hoplias lacerdae and Cyprinus carpio) during normoxia and graded hypoxia. In these species, hypoxic bradycardia consistently occurred during severe hypoxia (below the critical oxygen tension--PCO2) and was accompanied by alterations in the ECG recordings. Three basic ECG alterations were demonstrable: 1) increase in the T wave area and amplitude, being more positive and with symmetrical morphology during severe hypoxia (P. mesopotamicus); 2) negative T wave in normoxia, changing to isodiphasic (just above the PCO2) and positive (below the PCO2; H. malabaricus and H. lacerdae); 3) positive T wave in normoxia, changing to negative in severe hypoxia (5 mmHg; Cyprinus carpio). These findings indicate changes in the direction of ventricular repolarization during exposure to severe hypoxia, and the analysis of the ECGs in relation to the derivation line permitted the estimation of these drifts to be 17 degrees in P. mesopotamicus, 46 degrees in H. malabaricus, 43 degrees in H. lacerdae, and 32 degrees in C. carpio. The changes in the direction of ventricular repolarization were attributed to myocardial impairment due to insufficient oxygen supply, and support the idea of a relationship between cardiac dysfunction and the bradycardia developed during severe hypoxia.

The results of 182 genetic amniocenteses between 14 and 37 weeks gestation, from 1986 to 1992, and of two cordocenteses in 1992, are reported. There were two main reasons for referral: maternal age 35 years and older and abnormal ultrasound assessment. Fetal cells were closed cultured and mass harvested. In 3.7% of cases fetal chromosomes were defective. Turn around time was about three weeks up to and including 1991 and two weeks in 1992, culture failure rate was 7% that year. No cytogenetic misdiagnosis and no complication or sequelae related to the amniocenteses were detected. We conclude this is a safe and reliable procedure to obtain fetal karyotypes and to improve obstetric management of high-risk pregnancies.

O6-methylguanine-DNA methyltransferase (MGMT) activity was measured in 68 tissue samples taken from brain. A wide range in activity among samples was observed, with all nonmalignant samples showing transferase activity (Mer+) but approximately 15% of WHO grade II low-grade astrocytomas and WHO grade IV glioblastoma multiformes lacking activity (Mer-). On average, astrocytomas and glioblastomas showed less transferase activity than either nonmalignant tissue or meningiomas. Monoclonal antibodies specific for MGMT showed both cytoplasmic and nuclear staining of Mer+ brain tumor cells in culture but no staining of Mer- cells in culture. In pathology specimens from anaplastic astrocytomas, glioblastoma multiformes, and meningiomas, antibody staining revealed both cytoplasmic and nuclear MGMT, while one sample showed little or no MGMT-specific staining. These results help explain why nitrosoureas have been among the most successful agents in treatment of brain tumors and indicate the subcellular localization for the repair activity, which may be relevant to nitrosourea resistance.

Poly (L-lactide)-poly (oxyethylene)-poly (L-lactide) block copolymers obtained in bulk, by a ring opening mechanism, from poly (ethylene glycol)s (PEG)s and L-lactide (LA), at 120–140°C, in the absence of added catalysts are described. By using PEGs with different molecular masses, 3000 and 35000, respectively, and varying the initial molar ratio LA to PEG, two series of copolymers with different molecular masses, relative length of blocks and hydrophilicity were obtained. Physico-chemical characterization of the copolymers had been previously performed. The morphological characteristics of the copolymers were investigated by means of X-ray diffractometry, optical and scanning electron microscopy. The biological properties of the materials were determined by evaluating their cytotoxicity, cytocompatibility, hemocompatibility and degradability using different standard tests. The results obtained indicate that the block copolymers synthesized may be useful for biomedical applications, in particular as resorbable drug vehicles. The materials are brittle and their mechanical properties are not appropriate for implant devices.

Background: Patients with breast cancer frequently develop bone metastases, which are responsible for high morbidity and mortality. It is known that numerous molecules are involved in the bone metastasization process and that only cancer cells with a specific molecular profile are capable of reaching and colonizing bone tissue. The early detection of patients with a high probability of relapsing to bone could be used to select candidates for tailored therapy with bone-specific drugs such as bisphosphonates or RANK-L inhibitors. The aim of the present study was to identify a pattern of tissue markers from primary breast cancer capable of predicting bone metastatization. Material and methods: The expression of different markers was retrospectively analyzed in frozen breast cancer tissue samples from 40 patients comprising 15 cases with no evidence of disease (NEDP), 15 with bone metastases (BMP), and 10 with visceral metastases (VMP). Twelve transcripts were analyzed by Quantitative Real time PCR: trefoil factor 1(TFF1), DKK1, bone sialoprotein (IBSP), heparanase (HPSE), osteopontin (SPP1), Agr2, SPARC, CTGF, COMP, follistatin (FST), osteoprotegerin and RANK. The predictive accuracy of each marker was calculated using receiver operating characteristic (ROC) curves. Results: Analysis of marker expression in the 3 different subgroups showed twofold higher median values of COMP and HPSE in BMP with respect to either NEDP or VMP (no significant difference). Furthermore, TFF1 median value was about sevenfold higher in BMP than in the other 2 subgroups (p=0.05). The area under the curve (AUC) was 0.73 for TFF1 and 0.62 for COMP and HPSE. Considering markers as dichotomous variables, TFF1 expression in BMP reached 67% compared to 21% and 20% in NEDP and VMP, respectively. In dichotomous variable analysis, the most important result was observed for TFF1; in particular, TFF1 positivity was observed in 67% of cases in the BMP subgroup compared to only 21% and 20% in NEDP and VMP, respectively. The combination analysis of TFF1 and other markers showed that positivity to at least one of the three markers, TFF1, DKK1, or IBSP, was observed in 80% of cases for the BMP group, and in only in 21% and 20% of cases in NEDP and VMP subgroups (p=0.041). Another interesting marker was RANK: although sensitivity was fairly low (12%), specificity reached 100% in both control groups. Conclusions: Our preliminary study identified a RT-PCR gene expression pattern in primary breast cancer that could predict patients destined to bone relapse. Such patients could consequently benefit from adjuvant treatment with bone-targeted therapy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-15.

e21030 Background: The process of bone metastasization includes numerous steps such as proliferation, invasion and adhesion, involving molecules, growth factors, chemochines and their receptors tha...