Onsager's irreversible thermodynamics of the dynamics of transient pores in spherical lipid vesicles.

Onsager's irreversible thermodynamics is used to perform a systematic deduction of the kinetic equations governing the opening and collapse of transient pores in spherical vesicles. We show that the edge tension has to be determined from the initial stage of the pore relaxation and that in the final state the vesicle membrane is not completely relaxed, since the surface tension and the pressure difference are about 25% of its initial value. We also show that the pore life-time is controlled by the solution viscosity and its opening is driven by the solution leak-out and the surface tension drop. The final collapse is due to a non-linear interplay between the edge and the surface tensions together with the pressure difference. We also discuss the connection with previous models.

Appraisal of the difference between the mesiodistal diameters of deciduous incisors and molars and permanent teeth.

AIM: Difference in tooth size between deciduous and permanent teeth can resolve space problems during development of the dentition. AIM: To determine the difference in size between deciduous and permanent teeth in the anterior and posterior areas of the mouth in a group of school-age children from Medellin, Colombia. DESIGN: this longitudinal prospective, descriptive investigation was carried out in 139 skeletal Class I dental stone casts from school-age children from Medellin. Patients were followed annually from 6 to 12 years of age. The final sample consisted of 53 children (35 girls and 18 boys). Leeway space and the incisor liability were determined. RESULTS: A higher positive leeway space was found in the mandible than in the maxilla (3.622 mm and 1.556 mm, respectively). Incisor liability was negatively higher in the maxilla than in the mandible (-7.884mm and -5.386mm, respectively). Six patients showed a negative leeway space between -1.582 mm and -3.184 mm for the mandible and the maxilla, respectively. No statistical significant differences were found by gender; girls showed higher leeway space and incisor liability than boys. CONCLUSION: Normal values for one ethnic group should not be considered normal for another and each group must be treated according to its own characteristics.

Tomato and tomato byproducts. Human health benefits of lycopene and its application to meat products: a review.

During recent decades, the food industry, consumers, and regulatory authorities have developed a significant interest in functional foods because of their potential benefits for human health over and above their basic nutritional value. Tomato is the second most important vegetable crop in the world. The amount of the related wastes is estimated at up to 50,000 tons per year, representing a serious disposal problem with a consequent negative impact on the environment. Tomato byproducts contain a great variety of biologically active substances, principally lycopene, which have been demonstrated by in vitro and in vivo studies to possess antioxidant, hypolipidemic, and anticarcinogenic activities. The aim of this review is to present an overview of the functional and physiological properties of the principal bioactive compound present in tomato and tomato byproducts, lycopene, its addition to meat, and meat products.

[Evaluation of the collaboration between Primary and Hospital Care in order to improve inappropriate prescription]. / Evaluación de la colaboración entre atención primaria y hospitalaria para mejorar la polimedicación inapropiada.

INTRODUCTION AND OBJECTIVES: To evaluate the implementation of a collaborative experience between Primary (PC) and Hospital Care (HC) aimed at reducing potentially inappropriate prescribing (PIP) in patients with polypharmacy. MATERIALS AND METHODS: Collaborative experience including a controlled before-after intervention study, carried out in the Donostialdea Integrated Health Organization (IHO), with Bilbao Basurto IHO as control group, Osakidetza, Basque Health Service. Participant were 227 PC physicians and physicians from 7 hospital services, and patients with 5 or more drugs meeting at least one PIP criteria. The intervention consisted of communication and knowledge between professionals, PC-HC consensus, training, identification of patients at risk, medication review, evaluation and feed-back. The collaboration process (agreements, consensus documents, training activities) and the change in the prevalence of PIP in polymedicated patients (using computerised health records) were evaluated. RESULTS: A total of 21 PIP criteria and 6 recommendation documents were agreed. An analysis was performed on 15,570 PIP from OSI Donostialdea and 24,866 from the control group. The prevalence of PIP in polymedicated patients was reduced by -4.53% (95% CI: -4.71 to -4.36, P< .0001) in comparison with the control group. The before-after differences were statistically significant across the 7 services. CONCLUSIONS: PC-HC collaboration is feasible and, along with other intervention components, reduces inappropriate polypharmacy in the context of a recently integrated healthcare organisation. The collaboration process is complex and requires continuous monitoring, policy involvement, leadership that encourages health professional participation, and intensive use of information systems.

Are hepatocellular carcinoma surveillance programs effective at improving the therapeutic options.

AIM: to evaluate whether the current surveillance programs (ultrasonography and alpha-fetoprotein testing every six months) are successful in detecting patients in the early stages. MATERIAL AND METHODS: the health records of all patients diagnosed with hepatocellular carcinoma in Donostia Hospital between 2003 and 2005 were reviewed retrospectively. Eighty-five patients (11 women and 74 men) were included in the study and demographic data, risk factors and clinical data were obtained. Patients were split into two groups according to whether or not they had been included in a surveillance program. RESULTS: seventy per cent of patients of the surveillance group is diagnosed in early stage opposite to 26.7% of patients in no surveillance group (p < 0.05). Thirteen patients cannot receive curative treatment in spite of the diagnosis in early stage (9 in the surveillance group and 4 in the no surveillance group. The global sensibility of the surveillance program in our series is 95%. CONCLUSIONS: current hepatocellular carcinoma surveillance programs, which comprise six-monthly ultrasonography and alpha-fetoprotein tests, are highly sensitive and effective. These programs result in the detection of hepatocellular carcinoma in its early-stages, when potentially curative treatment may be offered.

[Massive intravascular hemolysis secondary to sepsis due to Clostridium perfringens]. / Hemólisis masiva intravascular secundaria a sepsis por Clostridium perfringens.

Massive hemolysis secondary to sepsis caused by Clostridium perfringens is a rare entity but appears fairly often in the literature. In nearly all published reports, the clinical course is rapid and fatal. We describe the case of a 75-year-old woman with diabetes who was admitted with symptoms consistent with acute cholecystitis. Deteriorating hemodynamics and laboratory findings were consistent with intravascular hemolysis, coagulation disorder, and renal failure. Gram-positive bacilli of the Clostridium species were detected in blood along with worsening indicators of hemolysis. In spite of antibiotic and surgical treatment, hemodynamic support and infusion of blood products, the patient continued to decline and died in the postoperative recovery unit 14 hours after admission. Mortality ranges from 70% to 100% in sepsis due to Clostridium perfringens, and risk of death is greater if massive hemolysis is present, as in the case we report. Only a high degree of clinical suspicion leading to early diagnosis and treatment can improve the prognosis. This bacterium should therefore be considered whenever severe sepsis and hemolysis coincide.

[Utility of various non-invasive methods for fibrosis prediction among Basque Country patients with phenotypic hemochromatosis]. / Utilidad de los diferentes métodos no invasivos de predicción de fibrosis hepática en pacientes del País Vasco con hemocromatosis fenotípica.

OBJECTIVE: To determine whether the product of multiplying age by liver iron concentration (LIC) (fibrosis index; cut-off, 480,000), platelets, transaminases, and ferritin values are related to the risk of high grade fibrosis. METHODS: A retrospective study of 32 patients with hereditary hemochromatosis (HH) with phenotypic expression. All patients had a liver biopsy with LIC. RESULTS: In 7 patients a magnetic resonance imaging (MRI) scan (1.5 T) was obtained with LIC following Alustiza's protocol. Liver biopsy: fibrosis grade (F) 0-2 in 23 patients; F 3-4 in 9. Fibrosis index (FI) showed a specificity of 68%, sensitivity of 85.7%, positive predictive value (PPV) of 42.8%, and negative predictive value (NPV) of 94.4% for high-grade fibrosis. Platelet count ( < 200,000) revealed a NPV of 94.7% for F3-4. Aspartate transaminase (AST) levels above the upper limit of normal showed a NPV of 94.4%; ferritin levels (> 1,000) a NPV of 75%, and MRI-derived LIC x age (> 480,000) a NPV of 80%. The combination of FI (either by biopsy or MRI) with transaminases, and of platelets with transaminases revealed a NPV of 100%. CONCLUSIONS: FI > 480,000 and platelets < 200,000 have the highest sensitivity for high-degree fibrosis prediction. A negative result allows to discard significant fibrosis in 94% of cases. MRI allows a good fibrosis prediction.

[Porphyria cutanea tarda. An analysis of HFE gene mutations, hepatitis viruses, alcohol intake, and other risk factors in 54 patients from Guipúzcoa, Basque Country, Spain]. / Porfiria cutánea tarda: asociación con mutaciones HFE, hepatitis virales, alcohol y otros factores de riesgo en Guipúzcoa, País Vasco.

AIM: To study the frequency of HFE gene mutations (C282Y, H63D, S65C) in a group of 54 sporadic PCT patients and in a group of healthy controls (blood donors) from Guipúzcoa, Spain. We studied the association of PCT with HCV, HBV, alcohol abuse, and other established risk factors. METHODS: The analysis of mutations was made by PCR. Allelic and genotypic frequencies were compared. Probability was determined and a Chi-squared test was performed. RESULTS: No association was observed between C282Y mutation and PCT (5.76 vs. 5% in controls). A high H63D mutation frequency was observed in PCT (34.25%) but was not statistically significant (controls 29.31%) because of the high prevalence of this mutation in the Basque general population. The S65C mutation was lower in PCT than in controls. There is a similar presence for H63D heterozygosis in PCT (38.8 vs. 38.8%). HCV association was observed in 35.18% of patients with PCT. HBV infected 7.4% of patients. Heavy alcohol intake (> 60 g/day) was present in 55.55% of patients. No HIV-infected patients were detected. The study of other risk factors revealed only one of the five women with PCT taking estrogens. CONCLUSION: Our results found no relevant role for C282Y and H63D mutations. External factors such as HCV and alcohol could be determinant in the development of PCT in the Basque population.

Phenotype and natural history of elderly onset inflammatory bowel disease: a multicentre, case-control study.

BACKGROUND: Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD). AIM: To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD. METHODS: Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset). RESULTS: One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). CONCLUSIONS: Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC.

Selective sphincteroplasty of the papilla in cases at risk due to atypical anatomy.

AIM: To analyze the indications, efficacy and safety of sphincteroplasty in our centre. METHODS: A retrospective study of sphincteroplasty in 53 cases of papilla at high risk was performed in 2004-2006. The procedure consisted of duodenoscopy with Olympus TJF 145 Videoduodenoscope, approach to the biliary tract using a catheter with a guidewire, and dilatation of the papilla with a dilatation balloon catheter using a syringe with a manometer for control of the filling pressure. RESULTS: The indications included intradiverticular papilla in 26 patients (49%), stenosis of a previous sphincterotomy in 19 patients (35.8%), small size of the papilla in 4 patients (7.5%), Billroth II gastrectomy in 3 patients (5.6%), and coagulopathy in one patient (1.9%). The efficacy was 97.8%, with all the calculi extracted from the common bile duct in 84.4% of the patients, even though 21 of the patients (39.6%) had calculi with a diameter equal to or greater than 10 mm. Seven patients (13.2%) presented complications: haemorrhage in 1 patient (1.9%) and mild pancreatitis in 6 patients (11.3%). The mean hospital stay in case of complications was of 3 +/- 0.63 d. CONCLUSION: Sphincteroplasty is highly effective, with a complication rate similar to that of sphincterotomy, furthermore, the complications are of low clinical importance. The use of the 10 mm balloon makes it possible to extract calculi with a diameter of over 15 mm and to extract more than 3 calculi without increasing the rate of complications and reduces the need to resort to lithotripsy or rescue sphincterotomy.

An ex vivo experiment to reproduce a forward fall leading to fractured and non-fractured radii.

Forward falls represent a risk of injury for the elderly. The risk is increased in elderly persons with bone diseases, such as osteoporosis. However, half of the patients with fracture were not considered at risk based on bone density measurement (current clinical technique). We assume that loading conditions are of high importance and should be considered. Real loading conditions in a fall can reach a loading speed of 2m/s on average. The current study aimed to apply more realistic loading conditions that simulate a forward fall on the radius ex vivo. Thirty radii from elderly donors (79y.o.±12y.o., 15 males, 15 females) were loaded at 2m/s using a servo-hydraulic testing machine to mimic impact that corresponds to a fall. Among the 30 radii, 14 had a fracture after the impact, leading to two groups (fractured and non-fractured). Surfacic strain fields were measured using stereovision and allow for visualization of fracture patterns. The average maximum load was 2963±1274N. These experimental data will be useful for assessing the predictive capability of fracture risk prediction methods such as finite element models.

MRI and endoscopic ultrasonography in the staging of gastric cancer.

OBJECTIVE: to determine the diagnostic precision of endoscopic ultrasounds (EUS) and magnetic resonance imaging (MRI) in the preoperative staging of gastric cancer. METHODS: a prospective, blind study was carried out in 17 patients diagnosed with gastric cancer (GC) using endoscopic biopsy from November 2002 to June 2003. Patients underwent preoperative MRI and EUS. The reference test used was pathology, and laparotomy for non-resectable cases. RESULTS: MRI (53%) was better than EUS in the assessment of gastric wall infiltration (35%). MRI (50%) was also superior to EUS (42%) for N staging. After pooling stages T1-T2 and T3-T4 together, results improved for both MRI (67 and 87.5%, respectively) and EUS (67 and 62.5%, respectively) (p < 0.05). N staging--lymph node invasion--results were correct in 50% for MRI as compared to EUS (42%). In classifying positive and negative lymph nodes EUS was superior to MRI (73 versus 54%). CONCLUSIONS: MRI was the best method in the assessment of gastric wall infiltration. EUS was superior to MRI for T1 staging, and in the assessment of lymph node infiltration.

[Recombinant activated factor VII in the postanesthetic recovery unit: review of 16 cases]. / Utilización del rFVIIa en una unidad de reanimación. Revisión de 16 casos.

We describe a series of 16 cases in which recombinant activated factor VII (rFVIIa) was used in our postanesthetic recovery unit. The mean age of the patients was 53.5 years (range, 30-84 years). Eleven were men and 5 women. The mean dose of rFVIIa used was 75 microg x kg(-1) (range, 60-90 microg x kg(-1)) and 25% of the patients needed a second dose. All the patients had postoperative bleeding, 62.5% after general surgery, 25% after a liver transplant, and 12.5% after a lung transplant. rFVIIa therapy was effective in 66% of the patients and no adverse thrombotic events related to treatment were observed. rFVIIa can be an efficacious therapeutic option for bleeding and coagulation disorders that are refractory to conventional replacement therapy. Approval to use rFVIIa in this setting and the establishment of indications should be based on further research.

[Prolonged response with paclitaxel after immunotherapy by pembrolizumab in lung cancer]. / Réponse prolongée sous paclitaxel après immunothérapie par pembrolizumab dans le cancer bronchique.

INTRODUCTION: Pembrolizumab, a humanized monoclonal antibody IgG4 anti-PD-1, having offered promising results in patients suffering from non-small cell lung cancer metastatic and heavily pretreated. OBSERVATION: We report here the case of an unexpected good response after pembrolizumab failure obtained with paclitaxel in a 68-year-old patient with stage IV lung adenocarcinoma. Moreover, the response duration with paclitaxel was more than fourteen months. CONCLUSION: Our case suggests a mutual potentiation of chemotherapy and immunotherapy, and raises the issue of the treatment sequence to favor.

Antioxidant and toxicological evaluation of a Tamarindus indica L. leaf fluid extract.

In the scientific community, there is a growing interest in Tamarindus indica L. leaves, both as a valuable nutrient and as a functional food. This paper focuses on exploring its safety and antioxidant properties. A tamarind leaf fluid extract (TFE) wholly characterised was evaluated for its anti-DPPH activity (IC50 = 44.36 µg/mL) and its reducing power activity (IC50 = 60.87 µg/mL). TFE also exhibited a high ferrous ion-chelating capacity, with an estimated binding constant of 1.085 mol L(-1) while its influence over nitric oxide production in human leucocytes was irregular. At low concentrations, TFE stimulated NO output, but it significantly inhibited it when there was an increase in concentration. TFE was also classified as a non-toxic substance in two toxicity tests: the acute oral toxicity test and the oral mucous irritability test. Further toxicological assays are needed, although results so far suggest that TFE might become a functional dietary supplement.

[Type III glycogen storage disease associated with hepatocellular carcinoma]. / Glucogenosis tipo III asociada a carcinoma hepatocelular.

Type III glycogen storage disease is a hereditary disorder with autosomal recessive transmission. It is characterized by accumulation of abnormal glycogen in the liver and, in 80% of patients, in muscle. The liver can also show fibrosis and sometimes cirrhosis. Until 2000, 9 cases of cirrhosis had been published, 3 of which showed associated hepatocarcinoma. We present the case of a 31-year-old woman, diagnosed in childhood with type III glycogen storage disease, who 30 years after onset developed a hepatocellular carcinoma with portal thrombosis in the context of advanced cirrhosis. This is the first case to be reported in the Spanish literature of type III glycogen storage disease associated with hepatocellular carcinoma.

Detection, classification and 3D reconstruction of biological macromolecules on hypercube computers.

In this work we present results of the mapping on hypercube computers of some of the key steps involved in the procedure for 3D structural determination from transmission electron microscopy images. The goal is the introduction of parallel processing tools in the field of electron microscopy image processing. We show how the rich topology of the hypercube, combined with an efficient programming strategy, allows for order-of-magnitude increase in computational capacity for such time-consuming tasks as calculation of multidimensional FFT's, cross-correlation coefficients, fuzzy partitioning functionals and the filtered back-projection 3D reconstruction method.

A fast Hough transform for segment detection.

The authors describe a new algorithm for the fast Hough transform (FHT) that satisfactorily solves the problems other fast algorithms propose in the literature-erroneous solutions, point redundance, scaling, and detection of straight lines of different sizes-and needs less storage space. By using the information generated by the algorithm for the detection of straight lines, they manage to detect the segments of the image without appreciable computational overhead. They also discuss the performance and the parallelization of the algorithm and show its efficiency with some examples.

[Liver alterations due to alpha-1-antitrypsin deficiency in adults. Study of 5 patients and analysis of the cases reported in the Spanish literature]. / Alteraciones hepáticas por déficit de alfa-1-antitripsina en adultos. Estudio de 5 pacientes y análisis de los casos publicados en la bibliografía española.

BACKGROUND: To determine the epidemiological characteristics of liver disease secondary to alpha-1-antitrypsin deficiency and associated processes in the Spanish population. PATIENTS AND METHOD: We reviewed the medical records of adults with liver abnormalities due to alpha-1-antitrypsin deficiency diagnosed between 1981 and 2001 in the Hospital Donosti in San Sebastian (Spain) as well as the cases published in the literature before 1999. Diagnosis was based on clinical and biochemical data, imaging tests and/or liver biopsy and/or necroscopy together with serum values of alpha-1-antitrypsin and phenotyping. RESULTS: Fifty cases of liver disease secondary to alpha-1-antitrypsin deficiency (45 from the literature and 5 from our hospital) were included. There were 34 men and 16 women aged between 18 and 77 years. Fifteen (30%) had relatives with alpha-1-antitrypsin deficiency. Hepatitis and/or neonatal cholestasis were confirmed in 4 and alcoholism was confirmed in 17. Of the series, 8 (16%) had portal fibrosis and 29 (58%) had cirrhosis. Cirrhosis was mainly macro-micronodular and was decompensated in 48% of the cases. Of the patients with cirrhosis, 12 were ZZ homozygotes and 12 were heterozygotes, mainly MZ and SZ. The most frequent associated process was respiratory disease (emphysema and/or chronic bronchitis) in 25 of the 50 cases (50%). CONCLUSIONS: The presence of cirrhosis in alpha-1-antitrypsin deficiency is low, approximately 2.2/100,000 for ZZ homozygotes. Age at diagnosis of cirrhosis or fibrosis was more than 50 years. The male-to-female ratio was 2 to 1. In one-third of the patients alcohol could have been a coadjuvant or aggravating factor in the liver disease. No differences were found between homo- and heterozygote phenotypes in patients with cirrhosis. The most frequently associated processes were respiratory diseases due to alpha-1-antitrypsin deficiency.