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Background: Losartan, one of the most frequently used drugs in Heart Failure (HF) treatment, could be modified for its bioavailability (BA) by generic formulations and other factors. Hence, the importance of therapeutic drug monitoring. Objective: Development and validation of a simplified analytical method using HPLC for simultaneous quantification of losartan and E-3174 in human plasma samples. The method was tested for determining the pharmacokinetics parameters of HF patients. Methods: Analytical conditions were optimized using a C18 column (4.6 X 50 mm, 3 μm. Thermo Scientific) at 25ºC. Conditions of mobile phase: a phosphate buffer (0.01M), adjusted to pH 2.5 with phosphoric acid (1M) and Acetonitrile (60:40 v/v). The flow rate was maintained at 1.2 mL/min, on a running time of 5 min and a sample injection volume of 50 μL. Absorbance for measurement of losartan and E-3174 was 200 nm. Pharmacokinetics profiles were determined with Phoenix Win- Nonlin 8.1 software in a non-compartmental model. Results: Analytical method developed and validated in this work is precise and accurate for simultaneous determination of losartan and E-3174 in human plasma samples in a range of 0.02 -10 μg/mL. In HF subjects, lower Tmax and higher Cmax for losartan and E-3174 patent than generic formulation were observed, which can be translated into less biological effect and more time to present it by the generic drug. Conclusion: The pharmacokinetic profile is dependent on the type of formulation studied (generic/ patent) hence the importance of conducting evaluations in our patients to ensure that the expected therapeutic effect is achieved with treatment administered.

OBJECTIVE To evaluate whether the concentration of serum lactate during the diagnosis of postpartum hemorrhage (bleeding ≥500 mL during labor or ≥1000 mL during cesarean delivery) predicts severe hemorrhage (SPPH; blood loss ≥1500 mL at end of labor or in the following 24 h). METHODS A prospective cohort pilot study was conducted of women with a vaginal or cesarean delivery from February 2018 to March 2019 who presented with bleeding ≥500 mL measured by the gravimetric method in a reference hospital in San Luis Potosi, Mexico. Venous blood samples were taken for analysis of serum lactate. A receiver operating characteristic curve determined the serum lactate threshold value for SPPH and χ2 test assessed the difference in serum lactate elevation between SPPH and non-SPPH groups. Lastly, the prognostic capacity between the thresholds was compared. RESULTS SPPH developed in 43.33% of the 30 women in the study group. The best prognostic threshold was 2.68 mmol/L of serum lactate (odds ratio [OR] 17.88, 95% confidence interval [CI] 2.7-16.8, P

Background: Up to 30% of the population has sleep disturbances, generating a negative health impact, a situation that is often not known and no medical attention is sought. It has been obs...

Objective To compare the resolution rate of hydrocephalus after endoscopy (predominantly endoscopic third ventriculostomy [ETV]) using flexible endoscopes during a 5-year period in patients with a permeable and a nonpermeable subarachnoid space (SAS). Material and Methods We conducted a retrospective cohort study of the videos and records of 150 hydrocephalic patients chosen randomly who underwent ETV (and other endoscopic procedures) with a flexible endoscope. The patients were classified into two groups based on the neuroendoscopic findings. The first group included patients with a permeable SAS, and the second group included patients with a nonpermeable SAS. A normal SAS or one with slight arachnoiditis was considered permeable. Adhesive arachnoiditis and immature or mechanically obliterated SASs were considered nonpermeable. Results We found a success rate of 70% in patients with a permeable SAS versus 33% in patients with a nonpermeable SAS. The baseline characteristics of both groups were homogeneous. We obtained a statistically significant difference (p Conclusion The permeability of the SAS is an important prognostic factor in the resolution rate of hydrocephalus after ETV (and other endoscopic procedures) using flexible neuroendoscopes. Therefore we recommend that the characteristics of the SAS be examined following every endoscopic procedure for hydrocephalus to identify patients at risk of recurrence.

The aim of this study was to compare the efficacy of preoperative and postoperative dexketoprofen trometamol for pain control after third molar surgery. Sixty subjects indicated for impacted mandibular third molar surgery were randomly assigned to two groups: preoperative (group 1, n = 30) and postoperative (group 2, n = 30) administration. Group 1 received 25 mg of dexketoprofen trometamol 30 min before surgery and 1 placebo capsule (same color and size with active drug) immediately after surgery. Group 2 received the placebo capsule 30 min before surgery and 25 mg of dexketoprofen trometamol immediately after surgery. Pain intensity was assessed using a numeric rating scale (NRS) during the first 8 h. The time of the need for a second dose of dexketoprofen trometamol, after the first administration, was recorded. The data were analyzed using mixed-model repeated-measures (MMRM), Wilcoxon rank-sum, and Kaplan–Meier analysis. After the 8 h period, no statistically significant difference was observed in the intensity of pain (MMRM, p = 0.41); and no significant difference in the time for a second dose (p = 0.956). In conclusion, preoperative administration of dexketoprofen trometamol is a reasonable clinical approach that is as effective as conventional postoperative pharmacological treatment, with the advantage of allowing early analgesia before pain develops. (ClinicalTrials.gov: NCT02380001 ).

Background: Research into long-term cause-specific mortality of women diagnosed with breast cancer is important because it allows for the splitting of the population into patients who eventually die from breast cancer and from other causes. The adoption of this approach helps to identify patients with an elevated risk of eventual death from breast cancer. Objective: The primary aim of this study was to examine the associations between both sociodemographic and clinicopathologic characteristics and the underlying risks of death from breast cancer and from other causes for women diagnosed with breast cancer. A second aim was to propose a predictive biomarker of cause-specific mortality in terms of treatment and several important characteristics of a patient. Methods: A cohort of 16 511 female patients diagnosed with breast cancer in 1990 was obtained from the Surveillance, Epidemiology, and End Results cancer registries and followed for 20 years. A mixture model for the regression analysis of competing risks was used to identify factors and confounders that affected either the eventual cause-specific mortality or conditional cause-specific hazard rates, or both. Missing data were handled with multiple imputation. Results: Curvilinear relationships of age at diagnosis along with race, marital status, breast cancer type, tumor size, estrogen receptor status, extension, lymph node status, type of surgery, and radiotherapy status were significant risk factors for the cause-specific mortality, with extension and lymph node status appearing to be confounded with the effects of both type of surgery and radiotherapy status. The score obtained from combining a set of predictors showed to be an accurate predictive biomarker. Conclusions: In cause-specific mortality of women diagnosed breast cancer, prognosis appears to depend on both sociodemographic and clinicopathologic factors. The predictive biomarker proposed in this study may help identifying the level of seriousness of the disease earlier than traditional methods, potentially guiding future allocation of resources for better patient care and management strategies.

Background and objectives: Dipeptidyl-Peptidase 4 (DPP-4) is a protein expressed in numerous cells and tissues. Recently it has shown its involvement as a catalyst in the inflammatory response in various pulmonary, autoimmune, intestinal and other pathologies. The objective of this study was to compare the preoperative serum levels of DPP-4 in patients with and without surgical finding of perivesicular inflammation. Materials and methods: a cross-sectional analytical study nested in a prospective cohort, including patients scheduled for elective cholecystectomy, without surgical complications, that were 18&ndash, 70 years of age, with low cardiovascular risk, without a history of peritonitis, pancreatitis, or jaundice and underwent ERCP protocol, type 2 diabetes mellitus, acute inflammatory (Protein C Reactive &lt, 3 mg/L, leucocytes &lt, 10 1000/mm3), neoplastic, nephrologic or liver disease, the use of anti-inflammatory drugs, steroids and/or antibiotics, the use of pacemakers or metallic implants and without major amputations and whom agreed to participate by providing their informed consent. Ethical and Research register: 45&ndash, 16. Prior to surgery we compiled anthropometric data and a blood sample to determine the serum levels of DPP-4. The presence of perivesicular inflammation was determined in the surgery. The data was analyzed using the statistical program Rstudio. Results: High BMI values were observed (27.8 &plusmn, 6.4), waist circumference (94.7 &plusmn, 15.1) and percentage of fat mass (34.7 &plusmn, 11.7), showing a cumulative frequency of 65.9% for overweight/obesity. In 27.3% of the interventions, intraoperative perivesicular inflammation findings were reported. The serum levels of DPP-4 were lower in the group of patients with perivesicular inflammation (3947.6 &plusmn, 1659.5 vs. 3053.2 &plusmn, 1469.6, LC95% of the difference: 160.4&ndash, 1628.3), being statistically significant (P = 0.018). Conclusions: In the subacute or chronic phases of cholecystitis, there appears to be a constant consumption of DPP-4, which would modulate a better immune response that could be related to the reduction of postoperative complications, so the use of Serum levels of DPP-4 as an early biomarker could improve the diagnostic accuracy of this pathology and the surgical approach.

Object The favorable effect of statin treatment after traumatic brain injury (TBI) has been shown in animal studies and is probably true in humans as well. The objective of this study was to determine whether acute statin treatment following TBI could reduce inflammatory cytokines and improve functional outcomes in humans. Methods The authors performed a double-blind randomized clinical trial in patients with moderate to severe TBI. Exclusion criteria were as follows: prior severe disability; use of modifiers of statin metabolism; multisystem trauma; prior use of mannitol, barbiturates, corticosteroids, or calcium channel blockers; isolated brainstem lesions; allergy to statins; previous hepatopathy or myopathy; previous treatment at another clinic; and pregnancy. Patients were randomly selected to receive 20 mg of rosuvastatin or placebo for 10 days. The main goal was to determine the effect of rosuvastatin on plasma levels of tumor necrosis factor–α, interleukin (IL)–1β, IL-6, and IL-10 after 72 hours of TBI. Amnesia, disorientation, and disability were assessed 3 and 6 months after TBI. Results Thirty-six patients were analyzed according to intention-to-treat analysis; 19 patients received rosuvastatin and 17 received placebo. The best-fit mixed model showed a significant effect of rosuvastatin on the reduction of tumor necrosis factor–α levels (p = 0.004). Rosuvastatin treatment did not appear to affect the levels of IL-1β, IL-6, and IL-10. The treatment was associated with a reduction in disability scores (p = 0.03), indicating a favorable functional outcome. Life-threatening adverse effects were not observed. Conclusions The authors' data suggest that statins may induce an antiinflammatory effect and may promote recovery after TBI. The role of statins in TBI therapy should be confirmed in larger clinical trials. Clinical trial registration no.: NCT00990028.

Background: Chronic kidney disease is a disorder of epidemic proportions that impairs cardiac function. Cardiovascular diseases are the leading cause of death in hemodialysis patients, and the understanding of new nontraditional predictors of mortality could improve their outcomes. Right ventricular systolic dysfunction (RVSD) has recently been recognized as a predictor of cardiovascular death in heart failure and hemodialysis patients. However, the factors contributing to RVSD in hemodialysis patients remain unknown. The aim of this study was to evaluate the clinical and echocardiographic factors associated with RVSD in hemodialysis patients. Methods: A cross-sectional study was conducted in which 100 outpatients with end-stage renal disease on chronic hemodialysis were evaluated. A transthoracic echocardiographic examination was performed at optimal dry weight. Right ventricular systolic function was evaluated using tricuspid annular plane systolic excursion (TAPSE). Clinical and echocardiographic data were recorded for each patient. A multivariate linear logistic regression was created using RVSD (TAPSE Results: Fifteen patients with RVSD and 85 patients without RVSD were analyzed. TAPSE had a positive correlation with left ventricular ejection fraction (LVEF) and myocardial relaxation velocity. Independent contributors to RVSD were LVEF (OR 1.14, 95% CI 1.05-1.26), left ventricular mass index (OR 1.02, 95% CI 1.00-1.04), and myocardial relaxation velocity (OR 1.81, 95% CI 1.18-3.19). Conclusions: Echocardiographic factors were significant contributors to RVSD. These measurements could be included as part of the routine workup in all end-stage renal disease patients on hemodialysis.

BACKGROUND Cholecystectomy has replaced open surgery and is regarded as the standard procedure today. The pneumoperitoneum needed to create working space can induce cardiovascular changes. Gasless laparoscopic surgery is effective; we evaluate a new retractor design. METHODS Patients older than 15 years with elective cholecystectomy and American Society of Anesthesiology I-II were consequently assigned to conventional or gasless surgery. We evaluated surgical time, hemodynamic stability, hours of hospital stay, and days of recuperation. RESULTS We analyzed 22 cholecystectomies, 10 by the gasless technique and 12 by gas laparoscopy. We did not observe significant differences in surgical time, length of hospital stay, or days of recuperation. However, surgical exposition time was longer in the retractor group than was expected by chance (P

Amnesia is a common sequela following traumatic brain injury (TBI), for which there is no current treatment. Pleiotropic effects of statins have demonstrated faster recovery of spatial memory after TBI in animals. We conducted a double-blind randomized clinical trial add-on of patients with TBI (16-50 years of age), with Glasgow Coma Scale (GCS) scores of 9-13, and intracranial lesions as demonstrated by computed tomography (CT) scan. We excluded those patients with recent head injury or severe disability; administration of known drugs as modifiers of statin metabolism; multisystemic trauma; prior use of mannitol, barbiturate, corticosteroids, indomethacin or calcium antagonists; surgical or isolated lesion in brainstem; allergy to statins; previous hepatopathy or myopathy; previous management in another clinic; or pregnancy. Each patient received the same treatment and was randomly allocated to receive either rosuvastatin (RVS) or placebo over a period of 10 days. The primary outcome measures assessed were amnesia and disorientation times using Galveston Orientation Amnesia Test. Additionally, we evaluated plasma levels of interleukin (IL) 1beta, tumor necrosis factor (TNF) alpha, and IL-6, as well as disability at 3 months. We analyzed eight patients with RVS and 13 controls with similar basal characteristics. Using Cox regression analysis, administration of RVS showed a reduction of amnesia time with a hazard ratio of 53.76 (95% confidence interval [CI], 1.58-1824.64). This was adjusted for early intubation, basal leukocytes, basal Marshall and Fisher score, change of IL-1beta levels, and lesion side. IL-6 values at day 3 were increased in the RVS group (p = 0.04). No difference was detected in disability at 3 months. While statins may reduce amnesia time after TBI, possibly by immunomodulation, further trials are needed in order to confirm this positive association.

Summary Introduction.To identify the laboratory and ultrasound factors that could predict the response to medical treatment of amoebic liver abscess. Material and method. Retrospective study of patients diagnosis with amoebic liver abscess in Hospital Central in San Luis Potosi, Mexico.We included patients greater than 15 years of both sexes. We excluded those with probable pyogenic abscess, immunosupression, history of abdominal, or biliary surgery, abdominal neoplasm abdominal or sepsis. We identified patients with good response to medical treatment and patients who needed the abscess drained.We studied the ultrasound findings, plasma levels of albumin, alkaline phosphatase, and bilirubin.

1. Information regarding the use of continuous i.v. administration of nitroglycerine as an antihypertensive agent in the management of pre-eclampsia is scarce. In the present study, i.v. nitroglycerine or sublingual nifedipine were administered to 32 women with severe pre-eclampsia who were being managed with controlled plasma volume expansion and MgSO(4) loading and maintenance doses. Maternal blood pressure and heart rate responses, fetal heart rate responses and perinatal fetal-maternal adverse effects were evaluated using classical parametric and non-parametric data analysis and data modelling by mixed models. 2. An important hypotensive response was observed in both groups, although this reponse was greater, faster and exhibited less variability (more precision) in the nitroglycerine-treated group. Heart rate also increased in both the nitroglycerine- and nifedipine-treated groups (4.6 +/- 4.4 vs 8.6 +/- 5.3 b.p.m., respectively), although the increase in the nifedipine-treated group was almost twofold that in the nitroglycerine-treated group. There were no significant changes in fetal heart rate in response to vasodilator therapy. The frequency of perinatal fetal-maternal adverse effects was similar in both groups at 40% and the adverse effects observed included flushing, headache, palpitations and nausea. 3. In conclusion, i.v. infusion of nitroglycerine is an effective, safe and alternative therapy for severe pre-eclampsia.

A self-tuning algorithm is presented for on-line insulin dosage adjustment in type 1 diabetic patients (chronic stage). The algorithm suggested does not need information of the patient insulin–glucose dynamics (model-free). Three doses are programmed daily, where a combination of two types of insulin: rapid/short and intermediate/long acting is injected into the patient through a subcutaneous route. The doses adaptation is performed by reducing the error in the blood glucose level from euglycemics. In this way, a total of five doses are tuned per day: three rapid/short and two intermediate/long, where there is large penalty to avoid hypoglycemic scenarios. Closed-loop simulation results are illustrated using a detailed nonlinear model of the subcutaneous insulin–glucose dynamics in a type 1 diabetic patient with meal intake.

The gold standard for quantifying insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp (Clamp) with a cut-off point of 5x10-2 (dL/min)/(microU/mL) or less to indicate insulin resistance. Bergman's minimal model (Min-Mod) is also being used to estimate IS, but there are doubts as to its equivalence with Clamp. The objective of the present study is to determine if Clamp and the tolbutamide and insulin techniques of Min-Mod are equivalent. Meta-analysis based on a bibliographic search from 1970 until the present was made for the MeSH terms: insulin resistance, hyperglycemic-clamp, euglycemic-clamp, Min-Mod, minimal model approach. Concordance was determined with both simple and intraclass correlation and Bland and Altman's concordance limits using R. Three of the 109 articles found were included. The concordance limits indicate that Clamp and Min-Mod are not equivalent, which could result in diagnostic errors if the accepted cut-off point is used for both methods. Given this lack of equivalence, a ROC analysis was performed and new diagnostic cut-off points of 2.4 and 4.6x0-2 (dL/min)/(microU/mL) for insulin and tolbutamide techniques of Min-Mod, respectively, are proposed, with adequate sensitivity, specificity, and predictive value. These values should be prospectively validated.

To identify the variables that predict the failure to treat amoebic liver abscesses.We prospectively carried out a case-control study on a cohort of patients who had been diagnosed with amoebic liver abscesses using clinical, ultrasonic, and serologic methods. Patients with pyogenic abscesses, negative ELISA tests for amoebiasis, immunosuppression status, or previous abdominal surgery were excluded. All patients received metronidazole, and those who demonstrated 4 days of unfavorable clinical responses received percutaneous or surgical draining of the abscess. Demographic, laboratory, and ultrasonographic characteristics were assessed as prognostic indications of failure.Of 40 patients with amoebic liver abscess, 24 (mean age: 36·7±11·2 years) responded to medical treatment and 16 (41·8±11·6 years) required drainage, including 14 patients who underwent percutaneous drainage and two patients who required surgery. The albumin level, abscess volume, abscess diameter, and alkaline phosphatase level were all statistically significant (P0·05) on the bivariate analysis. The highest (99%) sensitivity and negative predictive value were observed for an abscess volume500 ml and diameter10 cm, while the best specificity and positive predictive value were achieved with the combination of low serum albumin level, high alkaline phosphatase level, and large abscess volume or diameter.The prognostic indications of the failure to treat amoebic liver abscesses include low albumin, high alkaline phosphatase, and large abscess volume or diameter. The combination of these variables is a useful and easy tool for determining appropriate therapy.

Background Cardiovascular disease has been linked to endothelial progenitor cell (EPC) depletion and functional impairment in atherosclerosis and aortic stenosis. EPCs may play a pivotal role in vascular grafting. However, the EPC depletion in coronary artery bypass grafting (CABG) patients has not been compared to coronary artery disease-free valvular replacement patients with aortic stenosis. Methods We aimed to assess the basal number of CD34+/KDR+ and CD34+/CD144+ cells in CABG patients, compared to aortic stenosis valvular replacement patients. 100 patients (51 CABG and 49 valvular surgery ones) were included in the present study. All CABG or valvular patients had angiographic demonstration of the presence or the absence of coronary artery disease, respectively. Numbers of CD34+/KDR+ and CD34+/CD144+ were assessed by flow cytometry of pre-surgical blood samples. Results We found a lower number of CD34+/CD144+ cells in CABG patients compared to valvular patients (0.21 ± 0.03% vs. 0.47 ± 0.08%), and this difference remained statistically significant after the P was adjusted for multiple comparisons (P = 0.01428). Both groups had more EPCs than healthy controls. Conclusions Pre-surgical CD34+/CD144+ numbers are decreased in CABG patients, compared to valvular patients with absence of coronary disease., This work was supported by FISS (Health Research Fund, PI080920) and Red Tematica de Investigacion Cardiovascular RECAVA (RD06/0014/1007, RD06/0014/1027), both from the Instituto de Salud Carlos III (ISCIII). We are grateful to Fernando Ortego and all the nurses and doctors from the Cardiac Surgery service, Hospital Clinico San Carlos, for their technical assistance. We acknowledge support from Centro de Microscopía y Citometría (Universidad Complutense) and the Regional Blood Transfusion Centre, Madrid.

Silver nanoparticles (NNPs), alone or in combination with the bioadhesive Gantrez S-97, have demonstrated their efficacy against Streptococcus mutans; however, it is not known if this combination changes the color of teeth. The aim of this work was to measure the color changes occurring after the use of a Gantrez-NNP combination on enamel tooth blocks. Two study groups were randomly formed: enamel blocks brushed with a) the Gantrez-NNP combination and b) conventional toothpaste, for 1 minute once daily for 4 weeks, then rinsed with distilled water and placed in thymol solution. Color changes in the enamel blocks were measured using a Minolta colorimeter CR300. Analysis of mixed models was performed with R 2.10.1 at a 95%confidence level, using the nonlinear mixed effects (NLME) package. The results showed that there were no color changes over time, only a high luminosity equal in both groups. Our study showed that the use of the Gantrez-NNP combination is safe with respect to dental esthetics in the control of S. mutans.

Background and study aims Spontaneous intracerebral hemorrhage (ICH) represents the most fatal kind of stroke, and there is still no treatment available that improves the outcome. Statins are cholesterol reducers, and during the last few years many additional effects have been demonstrated that might be neuroprotective. We designed a pilot clinical study in order to evaluate whether the administration of statins is associated with a better outcome. Patients and methods From August to December 2006 we carried out a prospective/retrospective non-randomized clinical study. The prospective group was treated with rosuvastatin (20 mg) and the retrospective control group was taken from our clinical records with a relation of 1:3. We included patients of both sexes, aged > or =15 years with proven ICH in CT-scan. Exclusion criteria were a history of neoplasm, head injury four weeks before admission, non-hypertensive reasons, brainstem hemorrhage, steroid administration, cranial surgery, initial hydrocephalus, and NIHSS > or =30. Results We analyzed 18 patients treated with rosuvastatin and 57 controls with similar basic characteristics. The mortality rate during hospitalization was 1 (5.6%) patient in the statin group and 9 (15.8%) in the control group; the hazard ratio adjusted by the initial Glasgow Coma Scale (GCS), intubation, admission in intensive care unit, disruption into the subarachnoid space was 0.20 (95% CI 0.02-1.67). The odds ratio for NIHSS > or =15 at release was 0.04 (95% CI 0.003-0.93). Conclusions The use of statins during the acute phase of ICH could be associated with a better outcome. Further clinical trials are necessary to confirm a possible therapeutic effect and evaluate the toxicity of statins.

The objective of this study was to evaluate the prevalence and risk factors associated with candidiasis in chronic renal failure (CRF) and renal transplant (RT) patients. A cross-sectional study was made of 66 patients who were divided into 2 groups: group A (33 patients), RT patients, and group B (33 patients), who had been diagnosed with CRF. Data with respect to demographics, treatment type and duration, clinical laboratory results for blood leucocytes, oral hygiene, and diagnosis of oral candidiasis were collected. Risk factors associated with candidiasis were evaluated. Among the 66 patients, 21 showed microbiologic evidence of oral candidiasis; 12 of these were from the RT group and 9 were from the CRF patients. Children who were renally compromised (RT and CRF) presented a frequency of oral candidiasis of 31.82%, with no difference between study groups. C. albicans was the most frequently isolated species from RT and CRF patients. Duration of therapy and oral hygiene were the variables associated with the presence of oral candidiasis.

This paper presents an advisory/control algorithm for a type-1 diabetes mellitus (TIDM) patient under an intensive insulin treatment based on a multiple daily injections regimen (MDIR). The advisory/control algorithm incorporates expert knowledge about the treatment of this disease by using Mamdani-type fuzzy logic controllers to regulate the blood glucose level (BGL). The overall control strategy is based on a two-loop feedback strategy to overcome the variability in the glucose-insulin dynamics from patient to patient. An inner-loop provides the amount of both rapid/short and intermediate/long acting insulin (RSAI and ILAI) formulations that are programmed in a three-shots daily basis before meals. The combined preparation is then injected by the patient through a subcutaneous route. Meanwhile, an outer-loop adjusts the maximum amounts of insulin provided to the patient in a time-scale of days. The outer-loop controller aims to work as a supervisor of the inner-loop controller. Extensive closed-loop simulations are illustrated, using a detailed compartmental model of the insulin-glucose dynamics in a TIDM patient with meal intake.

The purpose of this study was to evaluate pain perception rates in pediatric patients by comparing computerized injection device and traditional injection procedure. In a clinical trial, by using a crossover design, sixty-four patients were randomly assigned to receive, in consecutive sessions, dental anesthetic techniques with either traditional or computerized device. Visual Analogue Scale qualification and heart rate monitoring as physiologic indicator of pain response were used for the evaluation. Results showed that traditional syringe injections were more painful than computerized injection device (p

This paper presents the design methodology for Mamdani-type fuzzy logic controllers to regulate the blood glucose level in a Type I diabetic patient. The overall control strategy is based on a two-loop feedback strategy. The inner-loop provides the amount of both rapid (Lispro) and slow (NPH) insulin types that the patient has to program in a three-shoots daily basis. The combined preparation is then injected to the patient through a subcutaneous route. Meanwhile, the outer-loop adjusts the maximum amounts of insulin provided to the patient. In this way, it is pursued to optimize the amount of insulin required to maintain a normal glucose level. Both controllers were synthesized gathering information about physician treatment of diabetic patients using fuzzy logic.

Endothelial progenitor cell (EPC) dysfunction is an important mediator of vascular disease in diabetes. We aimed to elucidate the mechanism of adhesion of EPC to diabetic and non-diabetic arteries and to study the effect of the anti-diabetic drug pioglitazone. Peripheral blood mononuclear cells were isolated from healthy donors. Human internal mammary arteries (HIMA) were isolated from patients who underwent coronary artery bypass surgery. EPC were labelled with 111In-oxine and perfused to HIMA in a perfusion chamber. Stromal derived factor-1 (SDF-1) and cyclooxygenase-2 (COX-2) were assessed by immunohistochemical analysis. CXCR-4 expression was assessed by flow cytometry. Adhesion of EPC was increased in HIMA from diabetic patients and was reduced after preincubation with 15 mM glucose for 72 h. EPC adhesion and CXCR-4 expression were inversely correlated. COX-2 and SDF-1 immunostaining in HIMA were positively correlated. Pioglitazone (1 microM) increased the adhesion of EPC to HIMA and the expression of CXCR-4 in EPC. Therefore, EPC-recruiting capability is increased in diabetic arteries, although EPC adhesion is notably impaired by high glucose concentrations. Interestingly, pioglitazone treatment enhances EPC adhesiveness.

Background Inflammation is a common feature in the majority of cardiovascular disease, including Diabetes Mellitus (DM). Levels of pro-inflammatory markers have been found in increasing levels in serum from diabetic patients (DP). Moreover, levels of Cyclooxygenase-2 (COX-2) are increased in coronary arteries from DP. Methods Through a cross-sectional design, patients who underwent CABG were recruited. Vascular smooth muscle cells (VSMC) were cultured and COX-2 was measured by western blot. Biochemical and clinical data were collected from the medical record and by blood testing. COX-2 expression was analyzed in internal mammary artery cross-sections by confocal microscopy. Eventually, PGI2 and PGE2 were assessed from VSMC conditioned media by ELISA. Results Only a high glucose concentration, but a physiological concentration of triglycerides exposure of cultured human VSMC derived from non-diabetic patients increased COX-2 expression. Diabetic patients showed increasing serum levels of glucose, Hb1ac and triglycerides. The bivariate analysis of the variables showed that triglycerides was positively correlated with the expression of COX-2 in internal mammary arteries from patients (r2 = 0.214, P Conclusions We conclude that is not the glucose blood levels but the triglicerydes leves what increases the expression of COX-2 in arteries from DP.