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Biomedical subjects

A de la Peña

Publications and source records attributed to A de la Peña.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy and safety of preprandial human insulin inhalation powder versus injectable insulin in patients with type 1 diabetes.

AIMS/HYPOTHESIS: The efficacy and safety of human insulin inhalation powder (HIIP) plus insulin glargine were compared to subcutaneously injected insulin (SC insulin) plus insulin glargine in patients with type 1 diabetes. METHODS: This was a randomised, open-label crossover study in which one group of patients received preprandial HIIP plus insulin glargine for 12 weeks, followed by the same duration with preprandial SC insulin (lispro or regular) plus insulin glargine. Another group of patients received the reverse treatment sequence. The trial was designed as a non-inferiority comparison of the two treatments for effect on HbA(1c); blood glucose levels were also monitored. Safety assessments included adverse event reporting and hypoglycaemic events. RESULTS: HbA(1c) at endpoint was 7.95+/-0.12% for the HIIP treatment and 8.06+/-0.12% for the SC insulin treatment; mean changes from baseline to endpoint were -0.08 and 0.00%, respectively, (p=NS). The upper limit of the 95% CI of mean difference in HbA(1c) between the two treatments was 0.02%, indicating that HIIP was not inferior relative to SC insulin, as measured against the pre-defined margin of 0.3%. Fasting blood glucose was significantly lower for HIIP treatment (8.09+/-0.33 mmol/l; n=117) than for SC insulin treatment (9.05+/-0.33 mmol/l; n=111) (p=0.01). Safety profiles were comparable between the two treatments. The rate of any hypoglycaemia (least-squares mean adjusted for 30 days+/-SE) was 8.9+/-0.7 and 8.2+/-0.8 for HIIP and SC insulin treatments, respectively, (p=0.29). The rate of nocturnal hypoglycaemia was greater for HIIP (4.2+/-0.4) than for SC insulin (2.7+/-0.4; p<0.001). CONCLUSIONS/INTERPRETATION: HIIP was similar in efficacy to SC insulin for glycaemic control in type 1 diabetes mellitus. The two treatments had comparable safety profiles.

Administration, Inhalation↗
PubMed2006

Exenatide: effect of injection time on postprandial glucose in patients with Type 2 diabetes.

AIMS: Exenatide is an incretin mimetic whose effect on glycaemic control in patients with Type 2 diabetes is currently under investigation. This study assessed the effect of injection time relative to a standardized meal on postprandial pharmacodynamics of exenatide in patients with Type 2 diabetes. METHODS: Eighteen patients participated in this single-centre, open-label, placebo-controlled, randomized, six-way crossover study. Patients received subcutaneous injections of either placebo (-15 min) or 10 microg of exenatide at -60, -15, 0, +30 or +60 min relative to a standardized breakfast meal on six consecutive days. Serial blood samples were assayed for plasma glucose and insulin concentrations. RESULTS: For all exenatide treatments, incremental postprandial glucose area under the postprandial plasma glucose curve from zero to 6 h (AUC0-6 h) was significantly reduced compared with placebo. When exenatide was administered before (-60, -15 min) or with the meal (0 min), peak postprandial glucose concentrations were significantly decreased (P < 0.0001 for all treatments) compared with placebo. Post-meal exenatide administration (+30, P < 0.05; +60 min, P = 0.21) resulted in smaller peak glucose reductions and in some patients transient low plasma glucose concentrations were reported. Peak plasma insulin concentrations in the pre-meal treatments were significantly lower than placebo (P < 0.05 for all treatments), while post-meal dosing groups exhibited a trend towards higher insulin peaks compared with placebo. The most common adverse events related to exenatide were headache, nausea, dyspepsia and vomiting, and were generally of mild-to-moderate intensity. CONCLUSIONS: In this study, all exenatide treatments demonstrated reductions in postprandial plasma glucose excursions compared with placebo. Pre-meal and with meal administration of exenatide produced greater reduction of postprandial glucose excursions compared with post-meal administration. These data support flexible dosing of exenatide at any time within 60 min before a meal.

Area Under Curve↗
PubMed2005

Control of hypertension in patients at high risk of cardiovascular disease.

BACKGROUND: Hypertension is a major cardiovascular risk factor, but knowledge about the real magnitude of the problem and its determinants is lacking. AIM: To assess control of hypertension and evaluate medical resource use, in patients at high risk of cardiovascular disease. DESIGN: Multicentric cross-sectional study. METHODS: We collected data for 2205 adult patients from 36 centres, representative of all regions of Spain. Patients had attended out-patient clinics from July 2002 to August 2003, had an absolute cardiovascular risk > or =20% at 10 years (according to the Framingham guidelines), and had a diagnosis of hypertension. Pregnant and terminally ill patients were excluded. RESULTS: Hypertension was inadequately controlled in 1384 patients (62.8%). LDL cholesterol was higher in patients with uncontrolled hypertension (median 130.2 vs. 120.0 mg/dl, p < 0.001). Haemoglobin A(1c) in diabetic patients was also greater in those with uncontrolled hypertension (median 7.10% vs. 6.90%, p = 0.010). Uncontrolled hypertension was associated with the following variables, in descending strength of association: higher LDL cholesterol, taking antihypertensive medication, living in non-metropolitan areas, and higher body mass index. DISCUSSION: Hypertension is poorly controlled in most patients with a high risk of cardiovascular disease. Uncontrolled hypertension is frequently associated with poor control of other risk factors.

Aged↗
PubMed2005

[Comparison of the effectiveness of pentobarbital and thiopental in patients with refractory intracranial hypertension. Preliminary report of 20 patients].

OBJECTIVE: To assess the effectiveness of pentobarbital and thiopental to control raised intracranial pressure (ICP), refractory to first level measures, in patients with severe traumatic brain injury. MATERIAL AND METHODS: Prospective, randomized study to compare the effectiveness between two treatments: pentobarbital and thiopental. The patients will be selected from those admitted to the Intensive Care Unit with a severe traumatic brain injury (postresuscitation Glasgow Coma Scale equal or less than 8 points) and raised ICP (ICP>20 mmHg) refractory to first level measures according to the Brain Trauma Foundation guidelines. The adverse effects of both treatments were also collected. RESULTS: We present the results of the first 20 patients included. Ten received pentobarbital and the other ten thiopental. There were no statistically significance differences in patients'characteristics (age, sex, severity of the trauma at admission and comorbilities). There were no differences between both groups neither in the Glasgow Coma Scale at admission (thiopental six points; pentobarbital seven points; P=0.26) nor in the admission Cranial Tomography, according to the Traumatic Coma Data Bank Classification. Thiopental treatment controlled raised ICP in five cases and pentobarbital in two cases (P=0.16). Five patients in the thiopental group died and eight in the pentobarbital group (P=0.16). There were no statistically differences between both groups regarding to the presence of hypotension (P=1) or infectious complications. CONCLUSIONS: These preliminary results indicate that thiopental could be more effective than pentobarbital in patients with refractory intracranial hypertension. These results support previous experimental findings that show that both treatments are not equal and justify to continue this study.

Adult↗
PubMed2002

LMP2 and LMP7 gene polymorphism in Mexican populations: Mestizos and Amerindians.

Low molecular weight polypeptide (LMP) genes are located within the major histocompatibility complex and have been associated with autoimmune diseases such as ankylosing spondylitis. In order to define the distribution of LMP genes in Mexican populations, the LMP2 and LMP7 polymorphism was analyzed in 312 Mexican individuals (95 Mexican Mestizos, 48 Nahuas, 56 Mazatecans, 50 Teenek, and 63 Mayos) belonging to different ethnic groups. In Mexican populations both Mestizos and Amerindians presented similar distribution of LMP2 and LMP7 polymorphisms, except Nahuas and Mayos who presented the higher frequencies of LMP2-H/H and the lowest frequencies of LMP2-H/R genotypes (P < 0.05 when compared with Mexican Mestizos). The LMP7-K/K genotype was absent in Nahuas, Teenek and Mayos and only one Mazatecan individual presented this genotype. Differences with other populations were found in Mexicans. An increased frequency of LMP2-H and a decreased frequency of LMP2-R alleles were observed in Mexican Amerindians (Nahuas and Mayos) when compared with Brazilian Amerindians (Kaingang and Guarani) and Caucasians (Spaniards) (P < 0.05). All Mexican populations (Mestizos and Amerindians) presented an increased frequency of LMP7-Q allele and a decreased frequency of LMP7-K allele when compared to Brazilian Amerindians (Kaingang), Caucasians (United States) and Asian (Japan) populations (P < 0.05). Genetic distances showed that Mexican Mestizos have an important relation with Spaniards and with all Mexican Amerindians. The present data corroborate the influence of Spaniard and Amerindian genes in the Mexican Mestizo population and could help to define the true significance of LMP polymorphism as genetic and evolutive marker in the Amerindian populations.

Biological Evolution↗
PubMed2001

[Thallium-201 scintigraphy and dobutamine echocardiography in the assessment of myocardial viability].

BACKGROUND: The possibility of differentiating viable from non-viable tissue among patients with severe coronary artery disease and severe left ventricular impairment entails relevant clinical and therapeutic implications since it may influence the indication of patient revascularization. To evaluate the presence of myocardial viability two techniques are available in the clinical setting: echocardiography with intravenous infusion of dobutamine and scintigraphy with myocardial perfusion with thalliem-201 by means of single-photon emission tomography. OBJECTIVE: To compare prospectively the value of these techniques for detecting viable myocardium. MATERIAL AND METHODS: Thirty-five patients with severe coronary disease and severe left ventricular dysfunction were included in the study. All patients underwent an echocardiogram using incremental doses of dobutamine, from 5 up to 40 micrograms/kg/min in three-minute periods. For thallium-201 scintigraphy the rest redistribution protocol with delayed images at 4 hours was used. The criteria for detecting viability were: a) for thallium-201, the presence of redistribution in delayed images and normal uptake at rest, and b) for dobutamine echocardiography, a sustained improvement in regional motion, biphasic response, and worsening. RESULTS: By considering the segmental improvement post-revascularization as "gold standard" of viability, the statistically significant variables in a logistic regression model and, therefore, predictors of segmental functional recovery were the biphasic response and the sustained response for dobutamine echocardiography and normal uptake at rest and redistribution in the delayed images for thallium-201. Taken together, the result was significant for the biphasic response of dobutamine echocardiography. CONCLUSIONS: The biphasic response with dobutamine echocardiography is the echocardiographic pattern that best predicts the functional recovery of the ischemic myocardium. A normal uptake and redistribution at four hours is the only scintigraphic pattern that can predict functional improvement. Of both patterns, the biphasic response is the best predictor of the functional recovery of the dysfunctional myocardium.

Cardiotonic Agents↗
PubMed2000

Microdialysis in peripheral tissues.

The objective of this review is to survey the recent literature regarding the applications of microdialysis in pharmacokinetic studies and facilitating many other studies in peripheral tissues such as muscle, subcutaneous adipose tissue, heart, lung, etc. It has been reported extensively that microdialysis is a useful technique for monitoring free concentrations of compounds in extracellular fluid (ECF), and it is gaining popularity in pharmacokinetic and pharmacodynamic studies, both in experimental animals and humans. The first part of this review discusses the use of microdialysis technique for ECF sampling in peripheral tissues in animal studies. The second part of the review describes the use of microdialysis for ECF sampling in peripheral tissues in human studies. Microdialysis has been applied extensively to measure both endogenous and exogenous compounds in ECF. Of particular benefit is the fact that microdialysis measures the unbound concentrations in the peripheral tissue fluid which have been shown to be responsible for the pharmacological effects. With the increasing number of applications of microdialysis, it is obvious that this method will have an important place in studying drug pharmacokinetics and pharmacodynamics.

Adipose Tissue↗
PubMed1999

Antioxidant status and glutathione metabolism in peripheral blood mononuclear cells from patients with chronic hepatitis C.

BACKGROUND/AIMS: Oxidative stress could play a role in the pathogenesis of hepatitis C virus infection. We investigated the oxidant/antioxidant status in peripheral blood mononuclear cells from patients with chronic hepatitis C and controls. METHODS/RESULTS: Lipid peroxidation products and superoxide dismutase activity in peripheral blood mononuclear cells were higher in chronic hepatitis C patients than in healthy subjects while glutathione S-transferase activity was reduced in patients as compared to controls. Catalase, glutathione peroxidase and glutathione reductase were similar in chronic hepatitis C and normal individuals. No statistically significant differences were found between patients and controls with regard to glutathione levels in peripheral blood mononuclear cells, but 35% of patients with chronic hepatitis C showed values of glutathione and oxidized glutathione which were below and above, respectively, the limits of normal controls. Finally, the glutathione synthetic capacity of the cytosol of peripheral blood mononuclear cells was significantly higher in patients than in controls, indicating increased glutathione turnover in lymphocytes from patients with chronic hepatitis C. CONCLUSIONS: Oxidative stress is observed in peripheral blood mononuclear cells from chronic hepatitis C patients. This process might alter lymphocyte function and facilitate the chronicity of the infection.

Adult↗
PubMed1999

A type 5 acid phosphatase gene from Arabidopsis thaliana is induced by phosphate starvation and by some other types of phosphate mobilising/oxidative stress conditions.

Low phosphorous availability, a common condition of many soils, is known to stimulate phosphatase activity in plants; however, the molecular details of this response remain mostly unknown. We purified and sequenced the N-terminal region of a phosphate starvation induced acid phosphatase (AtACP5) from Arabidopsis thaliana, and cloned its cDNA and the corresponding genomic DNA. The nucleotide sequence of the cDNA predicted that AtACP5 is synthesised as a 338 amino acid-long precursor with a signal peptide. AtACP5 was found to be related to known purple acid phosphatases, especially to mammal type 5 acid phosphatases. Other similarities with purple acid phosphatases, which contain a dinuclear metal centre, include the conservation of all residues involved in metal ligand binding and resistance to tartrate inhibition. In addition, AtACP5, like other type 5 acid phosphatases, displayed peroxidation activity. Northern hybridisation experiments, as well as in situ glucuronidase (GUS) activity assays on transgenic plants harbouring AtACP5:GUS translational fusions, showed that AtACP5 is not only responsive to phosphate starvation but also to ABA and salt stress. It is also expressed in senescent leaves and during oxidative stress induced by H2O2, but not by paraquat or salicylic acid. Given its bifunctionality, as it displays both phosphatase and peroxidation activity, we propose that AtACP5 could be involved in phosphate mobilisation and in the metabolism of reactive oxygen species in stressed or senescent parts of the plant.

Acid Phosphatase↗
PubMed1998

Risk factors for recurrence of hepatitis C after liver transplantation.

Recurrent hepatitis C is a frequent complication after liver transplantation for hepatitis C virus-related cirrhosis, but risk factors related to its development remain ill defined. Twenty-three patients receiving a primary liver graft for hepatitis C virus-related cirrhosis and with an assessable biopsy performed at least 6 months after liver transplantation were studied retrospectively. The end point of this study was to look for risk factors associated with the development of histologic hepatitis C in the graft. Thirty-six major variables were studied, and those reaching significance by univariate analysis were included in a multivariate analysis. Eighteen patients (78%) developed posttransplant hepatitis C. On univariate analysis, six variables showed significant predictive value: increased immunosuppression for treatment of acute rejection; pretransplant hepatocellular carcinoma; cumulative doses of prednisone at 3, 6, and 12 months after transplantation; and mean blood trough levels of cyclosporine in the first 6 months posttransplantation. On multivariate analysis, two variables retained independent statistical significance as predictors of hepatitis C recurrence, namely receipt of antirejection therapy (P = .0087) and lower mean cyclosporine levels in the first 6 months after transplantation (P = .0134). Therefore, recurrence of hepatitis C after liver transplantation seems to be at least partially related to posttransplantation immunosuppressive therapy.

Adult↗
PubMed1998

Liver transplantation in cirrhotic patients over 60 years of age.

Although life expectancy in Spain is above seventy years, age over sixty is considered a relative contraindication for liver transplantation (LT) in most centers. The aim of this study was to assess the outcome of LT in patients over sixty years of age comparing them to patients under that age. From January 1992 to August 1995, 61 cirrhotic patients underwent LT at our institution; of them, 43 (group I) were younger than 60 years (mean +/- SEM: 51.9 +/- 0.9 years, range: 37-59) and 18 patients (group II) were 60 years or older (64.1 +/- 0.7, range: 60-71). Main pre-transplant variables (sex, etiology of liver disease, presence of hepatocarcinoma, Child-Pugh's score and renal function) were similar in both groups. The follow-up (median and range) for group I was 28 and 3-47 months, and for group II 16.5 and 3-48 months. Actuarial survival rates at one and four years post-LT were respectively 88.3% and 85.6% for group I, and 87.8% and 87.8% for the group II (p = n.s.). There were no differences between both groups regarding the incidence of rejection, major infections, neurologic complications, renal failure, pathological bone fractures, diabetes mellitus or hypertension. Nevertheless, cardiovascular complications were significantly more frequent in group II (p = 0.002) although they were not the cause of death. In conclusion, our results show that the outcome of LT in patients over sixty years old is comparable to that observed in patients under that age. LT should not be contraindicated on the only basis of an age greater than 60 years.

Adult↗
PubMed1997

The effects of the degree of surgical trauma and glucose load on concentration of thyrotropin, growth hormone and prolactin under enflurane anaesthesia.

Sixty patients undergoing gynecological surgery under enflurane nitrous-oxide anesthesia were studied. The goal was to investigate the effects of the degree of surgical trauma and glucose load on the pattern of TSH, GH and PRL secretion before, during and following surgery. For this purpose the patients were divided into four groups according to the severity of the operation and the type of fluid administered. The groups were as follows: group 1, major surgery--glucose solution; group II, major surgery--lactated Ringer solution; group III, minor surgery--glucose solution; group IV, minor surgery--no intravenous fluids. The three hormone concentrations, 45 min after the start of anesthesia, increased in all groups. The highest values for GH and PRL concentration were observed in group IV. This increase was followed by a decrease 24 h and 5 days after induction, at the end of the study, except in group IV where TSH and GH levels fell back to normal values more slowly. These results lead to the following conclusions: a) Enflurane does not suppress hormonal stress response to surgical trauma; b) A similar pattern is obtained for pituitary response, indicating that a general pituitary stimulus takes place in these situations; c) Glucose load plays an important role in pituitary hormonal response to surgical stress; d) There is no direct relationship between the degree of surgical trauma and the hormone levels in patients under enflurane anaesthesia.

Adult↗
PubMed1996

[The POEMS syndrome, apropos of 2 cases and review of the literature].

We describe two cases of POEMS syndrome, both with polyneuropathy, monoclonal gammopathy of the IgG lambda type, thickening of the skin with Raynaud phenomenon, multiple osteosclerotic lesions and hypothyroidism. One of them, also had papilledema, elevated cerebrospinal fluid protein, intracranial hypertension and phrenic nerve palsy; the other one had ascites and hepatosplenomegaly. Phrenic nerve palsy associated to this syndrome has not been described previously.

Ascites↗
PubMed1993

Rapid identification of Triticeae genotypes from single seeds using the polymerase chain reaction.

An easy and quick protocol has been developed for DNA analysis via PCR. Single cereal endosperm or small leaf pieces can be separately processed in several PCR reactions. The resultant PCR patterns are equivalent to those obtained with standard DNA extraction protocols using either specific or random primers. Intra- and inter-specific variability can be detected. This method allows the analysis of a large number of individuals in early stages prior to the plant sowing.

DNA↗
PubMed1993

Progressive intracranial occlusive disease associated with deficiency of protein S. Report of two cases.

BACKGROUND AND PURPOSE: Deficiency of the free fraction of protein S has been associated with arterial or venous stroke. The pathogenesis of vascular occlusion in patients with protein S deficiency is not known. We present two cases of cerebral infarction and deficiency of protein S in which the subjects had progressive intracranial occlusions. CASE DESCRIPTION: A 16-year-old girl was admitted because of left brain stem infarction and protein S deficiency. Cerebral angiography disclosed stenosis of the right intracranial vertebral artery and occlusion of the left posterior cerebral artery. A second angiogram performed 18 months later disclosed occlusion of the right vertebral intracranial artery. In the second case, a 17-year-old girl was admitted because of left hemispheric cerebral infarction and protein S deficiency. Cerebral angiography showed stenosis of the left anterior cerebral artery, left supraclinoid internal artery, and left middle cerebral artery. A second cerebral angiogram performed 5 months later disclosed occlusion of the left anterior cerebral artery and poor hemispheric perfusion through the left middle cerebral artery. CONCLUSIONS: Based on our cases, we postulate that some patients with prothrombotic states may develop progressive intracranial arterial occlusions, possibly secondary to a permanent thrombogenic stimulus. We suggest routinely searching for prothrombotic states in young patients with intracranial occlusion, especially if the occlusion is progressive and other causes are not obvious.

Adolescent↗
PubMed1992

The vascular plasminogen activator as source of the fibrinolytic potential observed during cardiopulmonary bypass.

Increased fibrinolytic activity is a well recognized constant finding observed during cardiopulmonary bypass (CPB). The purpose of the present work was to study and estimate the factors involved in the plasminogen activation and prekallikrein-kallikrein systems in a population of adult patients undergoing open heart surgery with CPB. Plasminogen activator activity determinations with a fibrinolytic method as well as plasminogen activation and prekallikrein-kallikrein determinations with synthetic substrates were carried out. Our results indicate that no active fibrinolysis but a fibrinolytic potential, similar to that observed in blood obtained after venous occlusion, can be demonstrated in circulating plasma during CPB. This fibrinolytic potential is related to the presence of vascular plasminogen activator released from endothelial cells by the CPB stimulus.

Adolescent↗