Search PubMed⌕ Search

Biomedical subjects

T Alarcón

Publications and source records attributed to T Alarcón.

At least 19 recordsLinked to original sources

Modelling cell growth and its modulation of the G1/S transition.

We present a model for the regulation of the G(1)/S transition by cell growth in budding yeast. The model includes a description of cell size, the extracellular nutrient concentration and a simplified model of the G(1)/S transition as originally reported by Chen et al. [Mol. Biol. Cell 11:369-391, 2000]. By considering cell growth proportional to cell size we show that the cell grows exponentially. In the case where cell growth is considered proportional to the concentration of a sizer protein within the cell, our model exhibits both exponential and linear cell growth for varying parameter values. The effects of varying nutrient concentration and initial cell size are considered in the context of whether progression through the cell-size checkpoint occurs. We consider our results in relation to recent experimental evidence and discuss possible experiments for testing our theoretical predictions.

Computer Simulation↗

Seropositivity to a major allergen of Anisakis simplex, Ani s 1, in dyspeptic patients with Helicobacter pylori infection: histological and laboratory findings and clinical significance.

Previous studies have demonstrated a high prevalence of seropositivity to the Ani s 1 protein in dyspeptic patients with Helicobacter pylori infection, but it is not known whether this represents episodes of anisakiasis misdiagnosis or previous exposure to the parasite without clinical relevance. To investigate the clinical significance of seropositivity to the Ani s 1 protein, a cohort study was performed with 87 consecutive dyspeptic patients who were treated for H. pylori infection. Fourteen (16.5%) patients were seropositive for the Ani s 1 protein, which was associated with the consumption of uncooked fish (p 0.0002). There were no differences in histological findings between subjects seropositive or seronegative for Ani s 1, but seropositive patients had increased eosinophil and basophil leukocyte counts (p < 0.05). Anti-Ani s 1 IgE was associated with a lack of improvement in the group of patients with non-ulcer dyspepsia after successful eradication of H. pylori (p 0.016). Thus, in at least a subset of patients with H. pylori infection, seropositivity to Ani s 1 could have clinical relevance. In addition, these data highlight that only anisakiasis associated with severe allergic or gastric symptoms is currently being diagnosed.

Adult↗

[Susceptibility of 36 Helicobacter pylori clinical isolates to four first-line antibiotics and virulence factors].

Helicobacter pylori possess various virulence factors, including cagA and vacA genes, that are associated with more aggressive symptoms such as bleed-ing ulcer and gastric cancer. Although there are different treatment regimens, there is still a failure rate of up to 20% due to antibiotic resistance, among other causes. In our country resistance to metronidazole and clarithromycin is increasing, especially in children, although they are still susceptible to amoxicillin and tetracycline. In order to determine the susceptibility pattern to these antibiotics 36 H. pylori clinical isolates were studied. MIC was determined by agar diffusion and agar dilution, and vacA and cagA genes were detected by conventional PCR. All isolates were susceptible to amoxicillin and tetracycline. Resistance to metronidazole by diffusion or dilution tests was 35.7% and 36.1%, respectively, and to clarithromycin, 21.4% and 22.3%, respectively. There was one strain that showed intermediate resistance to clarithromycin (MIC 0.38 mg/l), using agar diffusion, and that was included among the resistant strains. Three discrepancies were observed between the diffusion and dilution methods. The vacA s1 allele was detected in 17.2% of the strains, and vacA s2 in 82.8%; 51.7% of the total were cagA+. In conclusion, all strains tested in our study were susceptible to amoxicillin and tetracycline, allowing them to be considered as first-line antibiotics, while clarithromycin and metronidazole maintain a slight increase in their resistance level. The cagA+ strains were detected in expected quantities, while the s1 allele of the vacA gene was detected in lower quantities.

Adult↗

[Susceptibility pattern of Acinetobacter baumannii clinical isolates in Madrid vs. Hong Kong].

The objective of this study was to compare the susceptibility to seven antimicrobials of Acinetobacter baumannii clinical isolates from H. U. de La Princesa of Madrid vs. A. baumannii clinical isolates from Hospital Queen Mary of Hong Kong from January 2004 to March 2005. A total of 74 strains isolated from our hospital and 30 strains attended to Hospital Queen Mary were studied. The MIC (minimal inhibitory concentration) was determined by agar dilution method. NCCLS recommended breakpoints were used against imipenem, tobramycin, amikacin, ofloxacin and ceftazidime. For sulbactam the break point for ampicillin/sulbactam was used. BSAC breakpoint was considered against colistin. Colistin showed the highest susceptibility percentage in Spanish strains (98.64%), followed by imipenem (94.59%) and tobramycin (78.37%). About 50% of the clinical isolates were susceptible to sulbactam (54.05%) and amikacin (51.35%). The majority of the strains were resistant to ofloxacin (2.7% of susceptible strains) and ceftazidime (1.35% of susceptible strains). In the Hong Kong clinical isolates, high susceptibility percentages were shown for most antimicrobials: 96.66% to colistin, sulbactam, tobramycin and amikacin; lower for imipenem (93.33%) and ofloxacin (90%). Ceftazidime presented the lowest susceptibility percentage (10%). In conclusion, higher resistant percentages in Spanish strains than Chinese strains were obtained for most antimicrobials tested. To ofloxacin, 90% of Hong Kong isolates were susceptible while 93% of Madrid isolates were resistant. Geographically remote populations (such as Madrid and Hong Kong) showed important differences according to the susceptibility patterns.

Acinetobacter Infections↗

A mathematical model of Doxorubicin treatment efficacy for non-Hodgkin's lymphoma: investigation of the current protocol through theoretical modelling results.

Doxorubicin treatment outcomes for non-Hodgkin's lymphomas (NHL) are mathematically modelled and computationally analyzed. The NHL model includes a tumor structure incorporating mature and immature vessels, vascular structural adaptation and NHL cell-cycle kinetics in addition to Doxorubicin pharmacokinetics (PK) and pharmacodynamics (PD). Simulations provide qualitative estimations of the effect of Doxorubicin on high-grade (HG), intermediate-grade (IG) and low-grade (LG) NHL. Simulation results imply that if the interval between successive drug applications is prolonged beyond a certain point, treatment will be inefficient due to effects caused by heterogeneous blood flow in the system.

Cell Cycle↗

[In vitro activity of furazolidone and nitrofurantoin in Helicobacter pylori clinical isolates and study of mutation rate].

Clarithromycin, amoxicillin, tetracycline and metronidazole are the most frequently used antimicrobials for Helicobacter pylori infection treatment. While tetracycline and amoxicillin resistance are rare, clarithromycin and metronidazole resistance vary in different populations and are considered factors for treatment failure. The aim of this study was to determine the in vitro activity of furazolidone and nitrofurantoin in 164 H. pylori clinical isolates by agar dilution and to determine the spontaneous mutation rate. Metronidazole and clarithromycin resistance were 23.77% (CI95%: 18.96-29.14) and 16.78% (CI95%: 12.64-21.62), respectively; moreover, 1.4% (CI95%: 0.38-3.54) were intermediate to clarithromycin. All the isolates were susceptible to amoxicillin and tetracycline. Furazolidone and nitrofurantoin resistance rates were 1.82% (CI95%: 0.37-5.25) and 0.6% (CI95%: 0-3.35), respectively. The three furazolidone-resistant strains were nitrofurantoine-susceptible (MIC 4 mg/l for furazolidone and 2 mg/l for nitrofurantoin) and the nitrofurantoin-resistant strains were furazolidone-susceptible (MIC 4 mg/l for nitrofurantoin and 1 mg/l for furazolidone). These four strains were metronidazole-resistant (MIC 16 mg/l). Furazolidone or nitrofurantoin spontaneous mutants were not detected in the eight H. pylori strains tested. However, mutants with resistance to metronidazole were found with all the strains with a mutation rate of 7.4 x 10(-10) to 9.4 x 10(-10). Furazolidone and nitrofurantoin showed an excellent in vitro activity against the H. pylori clinical isolates included herein, supporting the usefulness of furazolidone as second-line antimicrobial after treatment failure or as first-line therapy in populations with low economical resources.

Anti-Infective Agents↗

A mathematical model of the effects of hypoxia on the cell-cycle of normal and cancer cells.

The evolution of the cell-cycle is known to be influenced by environmental conditions, including lack of extracellular oxygen (hypoxia). Notably, hypoxia appears to have different effects on normal and cancer cells. Whereas both experience hypoxia-induced arrest of the G1 phase of the cell-cycle (i.e. delay in the transition through the restriction point), experimental evidence suggests that only cancer cells undergo hypoxia-induced quiescence (i.e. the transition of the cell to a latent state in which most of the cell functions, including proliferation, are suspended). Here, we extend a model for the cell-cycle due to Tyson and Novak (J. Theor. Biol. 210 (2001) 249) to account for the action of the protein p27. This protein, whose expression is upregulated under hypoxia, inhibits the activation of the cyclin dependent kinases (CDKs), thus preventing DNA synthesis and delaying the normal progression through the cell-cycle. We use a combination of numerical and analytic techniques to study our model. We show that it reproduces many features of the response to hypoxia of normal and cancer cells, as well as generating experimentally testable predictions. For example our model predicts that cancer cells can undergo quiescence by increasing their levels of p27, whereas for normal cells p27 expression decreases when the cellular growth rate increases.

Animals↗

Community-acquired urinary tract infection caused by vancomycin-resistant Enterococcus faecalis clinical isolate.

We present a case of urinary tract infection caused by vancomycin-resistant Enterococcus faecalis. The patient is a 62-year-old woman showing no recent admittances. The isolated microorganism was identified by MicroScan (DADE) and API (BioMerieux) and susceptibility was assessed by disk diffusion, E-test and broth microdilution. The isolate was identified as Enterococcus faecalis and showed high MIC for vancomycin (>128 mg/l) and teicoplanin (8 mg/l) but was susceptible to ampicillin. The transmission routes of vancomycin-resistant enterococci in the community and their clinical implications remain uncertain. Healthy carriers have already been described in several countries but this case report represents an unusual finding.

Community-Acquired Infections↗

A cellular automaton model for tumour growth in inhomogeneous environment.

Most of the existing mathematical models for tumour growth and tumour-induced angiogenesis neglect blood flow. This is an important factor on which both nutrient and metabolite supply depend. In this paper we aim to address this shortcoming by developing a mathematical model which shows how blood flow and red blood cell heterogeneity influence the growth of systems of normal and cancerous cells. The model is developed in two stages. First we determine the distribution of oxygen in a native vascular network, incorporating into our model features of blood flow and vascular dynamics such as structural adaptation, complex rheology and red blood cell circulation. Once we have calculated the oxygen distribution, we then study the dynamics of a colony of normal and cancerous cells, placed in such a heterogeneous environment. During this second stage, we assume that the vascular network does not evolve and is independent of the dynamics of the surrounding tissue. The cells are considered as elements of a cellular automaton, whose evolution rules are inspired by the different behaviour of normal and cancer cells. Our aim is to show that blood flow and red blood cell heterogeneity play major roles in the development of such colonies, even when the red blood cells are flowing through the vasculature of normal, healthy tissue.

Animals↗

[Detection of resistance to clarithromycin in clinical isolates of Helicobacter pylori from children and adults].

Several methods have been used to detect clarithromycin resistance. Agar dilution is now recommended by the NCCLS (susceptible to clarithromycin: MIC<=0.25 mg/l; intermediate resistance: MIC=0.5 mg/l; resistant: MIC>=1 mg/l), and the detection of mutations involved in resistance is used in many laboratories. We analyzed 36 clarithromycin-resistant strains isolated from children and 30 from adults. In vitro susceptibility to clarithromycin was determined by an agar dilution method. DNA from the isolates was extracted using the method published by Ge and Taylor. A2142G and A2143G mutations were identified by PCR-RFLP. A 1.4 Kpb of the 23S rRNA gene was amplified and digested using MboII or BsaI restriction enzymes to detect mutations. The prevalence of the A-G transition mutation at position 2143 was higher in the children (80.55%) than in the adult patients (46.66%) (p<0.05); however, the prevalence of the mutation at position 2142 was higher in adults than in children (36.66% vs. 5.55%; p<0.05). In children, a higher MIC (2-64 mg/l) was observed when the A-G mutation was detected at position 2143. However, in adult patients higher MICs were observed when the A-G mutation was detected at position 2142.

Adult↗

[Susceptibility of Campylobacter jejuni clinical isolates from children to eight antibiotics].

This study aimed to identify the activity of eight antibiotics (ofloxacin, moxifloxacin, azithromycin, erythromycin, clindamycin, ampicillin, amoxicillin-clavulanic acid and tetracycline) against 80 strains of Campylobacter jejuni isolated from children. Minimal inhibitory concentrations (MIC) were determined by an agar dilution method. Resistance to azithromycin and erythromycin was considered when MIC > or =8 mg/l, to clindamycin when MIC > or =1 mg/l, to amoxicillin-clavulanic acid and ampicillin when MIC > or =32 mg/l, to ofloxacin and moxifloxacin when MIC > or =4 mg/l, and to tetracycline when MIC > or =16 mg/l. All strains tested were susceptible to amoxicillin-clavulanic acid. The lowest frequency of resistance was to azithromycin (2%), erythromycin (3.7%), clindamycin (4.4%) and ampicillin (4.9%), and the highest was to ofloxacin and tetracycline (61.7% for both), and moxifloxacin (37%). Considered the antibiotics of choice for the treatment of infections caused by this microorganism, macrolides showed excellent activity with MIC(90)=0.5 mg/l for azithromycin and MIC(90)=0.5 mg/l for erythromycin.

Amoxicillin-Potassium Clavulanate Combination↗

[In vitro activity of clarithromycin and metronidazole against Helicobacter pylori in different incubation atmospheres].

The aim of this study was to determine the in vitro activity of clarithromycin and metronidazole using an agar dilution method to compare two different incubation atmospheres: a CO2 incubator and a jar with a microaerobic gas-generating system. Antibiotics were placed on plates in twofold dilutions ranging from 128 to 0.064 mg/l in Mueller-Hinton agar supplemented with 7% horse blood. The inoculum was prepared from 31 Helicobacter pylori isolates and was inoculated using a Steers replicator. Plates were incubated for 3 to 5 days and MICs were recorded as the lowest concentration of antibiotic inhibiting visible growth. Two different incubation atmospheres were used: a CO2 incubator set at 95% humidity and 10% CO2, and a jar with a gas-generating envelope that produces 7-10% O2 and 14% CO2 (BioMerieux). Clarithromycin resistance was found in 19% of strains both in the gas-generating system and the CO2 incubator. Metronidazole resistance was 23% in both atmospheres. MICs for clarithromycin in both atmospheres showed two dilutions of difference for 100% of the strains, and were slightly higher in the jar with a gas-generating envelope. However, MICs for metronidazole were higher when it was incubated in the CO2 incubator, and in 86.7% of strains the MICs showed < or = 2 dilutions of difference. No great discrepancies were found for either metronidazole or clarithromycin using the two methods.

Anti-Bacterial Agents↗

Stochastic resonance in a suspension of magnetic dipoles under shear flow.

We show that a magnetic dipole in a shear flow under the action of an oscillating magnetic field displays stochastic resonance in the linear response regime. To this end, we compute the classical quantifiers of stochastic resonance, i.e., the signal to noise ratio, the escape time distribution, and the mean first passage time. We also discuss the limitations and role of the linear response theory in its applications to the theory of stochastic resonance.

Journal Article↗

[Geriatric management of the frail elderly with hip fracture may improve their clinical outcome].

BACKGROUND: The treatment of osteoporotic hip fracture requires the intervention of different medical specialties. The purpose of this study was to know the clinical profile of patients with an acute hip fracture referred for assessment and management to a geriatric assessment team (GAT) and the influence of this kind of geriatric care in their hospital outcome. PATIENTS AND METHOD: All patients 65 year-old or older admitted in a teaching hospital for a hip fracture in a 12 month period were included. The clinical, functional, cognitive and social status were assessed at admission and at discharge in both groups: the patients managed by the GAT and the patients that were not. The patients' characteristics of both groups were compared, and a multivariant analysis was applied to search the variables independently associated wit a better clinical course. RESULTS: On admission, the GAT patients (n = 202) were significantly (p < 0.05) older (84.4 vs 81.7 years), had more previous functional impairment (Barthel index 72 vs 79), more previous diseases (5.4 vs 3.3) and medications (3.2 vs 1.9), presented more frequency of cognitive impairment (52 vs 41%), of high surgical risk (54 vs 26%) and more need of social assistance at home (57 vs 38%) than non-referred patients (n = 200). At discharge, GAT patients had better functional status (Barthel index 38.5 vs 34), had been surgically treated (92 vs 84%), had received physiotherapy (83.7 vs 66.5%) and walked more (56.1% vs 33.8%) than others. In the multivariant analysis, the GAT intervention shows like an independent variable associated to higher frequency of surgical treatment (OR 4.21; CI, 2.80-6.34), to recovery of walking ability (OR, 8.26; CI, 5.23-13.04) and to receive more medical diagnosis (OR, 79.69; CI: 55.48-114.45). The GAT intervention was not associated to a longer hospital stay. CONCLUSIONS: The patients with hip fracture in acute phase required for management by a GAT are more complex than those who were not consulted. In these patients GAT intervention improve their clinical outcome and the efficiency of hospital admission.

Aged↗

Further experience of nonagenarians with hip fractures.

Our purpose was to investigate the factors after predictive outcome 3 months after the injury in terms of mortality and effective independent walking of nonagenarians with hip fracture. A prospective study was carried out for 2 yr in the orthopaedic wards on patients referred to geriatricians. The data were subjected to logistic regression forward stepwise analysis. Eighty-nine patients were included in the study; 55 (61.8%) had a trochanteric fracture and 86 required a surgical procedure. Before the fracture, 83 patients (93.3%) were able to walk by themselves or with minimal supervision. Forty-three patients (48.3%) had an American Society of Anaesthesiologists' of III-IV score. The mean number of postoperative complications was four. Mean hospital stay was 18.2 days. Within 3 months, 19 patients (21.3%) had died and 58 (69%) were living in their previous residence. Thirty-three (50% of living patients) were able to walk by themselves or with minimal help within 3 months of the fracture. Predictive variables for 3-month mortality were pre-fracture dependence on others for personal toilet and the presence of cognitive impairment. Predictive variables for independent efficient walking were bowel control and absence of cognitive impairment before the fracture, as well as no development of bed sores during hospitalization.These nonagenarian patients with hip fractures show low perioperative mortality, frequently return to their previous accommodation and present a limited recovery of walking ability.

Activities of Daily Living↗

A 9 year study of clarithromycin and metronidazole resistance in Helicobacter pylori from Spanish children.

The evolution of clarithromycin, metronidazole and amoxycillin resistance in 246 Spanish Helicobacter pylori clinical isolates, obtained from paediatric patients during a 9 year period, was determined by an agar dilution technique. Clarithromycin resistance (MIC 1 mg/L) was 2.27% (IC95 0.05-12.02) in 1991-1993, 20.98% (IC95 12.72-31.46) in 1994-1996 and 28.33% (IC95 20.48-37.28) in 1997-1999 (P < 0.01). Metronidazole resistance (MIC 8 mg/L) was 7.14% (IC95 1.49-19.48) in 1991-1993, 20.25% (IC95 12.04-30.79) in 1994-1996 and 43.90% (IC95 32.95-55.30) in 1997-1999 (P < 0.01). Amoxycillin resistance was not found (all strains showed MICs < 2 mg/L).

Anti-Bacterial Agents↗

[In vitro activity of linezolid against clinical isolates of methicillin-resistant Staphylococcus aureus].

In recent years, there has been a dramatic increase in the number of infections caused by multidrug-resistant Gram-positive microorganisms, making necessary the search for alternative antibacterial agents. Linezolid is a new synthetic antimicrobial agent with activity against multidrug-resistant Gram-positive cocci. The objective of this study was to determine the in vitro activity of linezolid against 74 clinical isolates of methicillin-resistant Staphylococcus aureus. Minimal inhibitory concentrations were determined by an agar dilution method following NCCLS criteria. Vancomycin, teicoplanin, rifampicin, trimethoprim-sulfamethoxazole and linezolid were studied at concentrations ranging from 128 to 0.008 mg/l. All of the isolates were susceptible to vancomycin, teicoplanin, and linezolid while four strains (5.4%) were resistant to rifampicin and five (6.7%) to trimethoprim-sulfamethoxazole. Linezolid showed excellent in vitro activity against 74 clinical isolates of methicillin-resistant Staphylococcus aureus with an MIC ranging from 0.25 to 2 mg/l

Acetamides↗