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Biomedical subjects

M López

Publications and source records attributed to M López.

At least 55 records · Page 3Linked to original sources

Cloning, purification and biochemical characterization of dipetarudin, a new chimeric thrombin inhibitor.

The development of thrombin inhibitors could provide invaluable progress for antithrombotic therapy. In this paper, we report the cloning, purification and biochemical characterization of dipetarudin, a chimeric thrombin inhibitor composed of the N-terminal head structure of dipetalogastin II, the strongest inhibitor from the assassin bug Dipetalogaster maximus, and the exosite 1 blocking segment of hirudin, connected through a five glycine linker. The cloning of dipetarudin was performed by a simple method which had not been used previously to clone chimeras. Biochemical characterization of dipetarudin revealed that it is a slow, tight-binding inhibitor with a molecular mass (M(r)=7560) and a thrombin inhibitory activity (K(i)=446 fM) comparable to r-hirudin.

Antithrombins↗

[Consequences of the bilateral vagus nerve section at a cervical level].

We present the consequences corresponding to a bilateral section of the main trunk of vagus nerve at cervical level in a patient with an oropharyngeal carcinoma with bilateral neck nodes. As a consequence of the bilateral resection of both vagus nerves during neck dissections, as well as motor and sensitive damage of the larynx and pharynx, we could observe affection of the normal tone of the oesophagus, stomach and duodenum which forced to enteral nutrition by direct jejunal access, and a disorder of the cardiac rhythm due to loss of the parasympathetic innervation appeared.

Bradycardia↗

Hepatitis C and the incidence of diabetes mellitus after renal transplant: influence of new immunosuppression protocols.

BACKGROUND: Hepatitis C has been associated with an increased incidence of diabetes mellitus (DM) following renal transplantation (RT). METHODS: Patients who underwent RT between 1985 and 2001 were excluded if they showed DM prior to RT, graft survival of less than 90 days, and unknown anti-HCV status (n=15). Two groups (G1 and G2) were distinguished according to the immunosuppressive regimen: G1 (transplanted 1985-1996) received steroids, azathioprine, and cyclosporine (n=330), whereas G2 (1997-2000) received new drugs in several combinations (MMF in 87% and/or tacrolimus in 35% [n=240]). Patients with HCV antibodies pre- and/or post-RT were considered HCV-positive. Post-RT DM requiring prolonged treatment with oral antidiabetics or insulin (>1 month) was assessed using Kaplan-Meier curves and Cox analysis. RESULTS: G2 patients were significantly older, had a greater body mass index (BMI), and suffered significantly less from acute rejection episodes during the first year than G1 patients. Furthermore, fewer required maintenance steroids. HCV-positivity was more common in G1 than in G2 (n=96, 29.1% vs n=27, 11.3%). Six G2 patients were successfully treated with interferon pre-RT, achieving negative PCR-HCV status (maintained post-RT). DM incidence at 4 years was similar in G1 and G2 (8.8% and 8.2%). G1 HCV-positive patients showed a greater risk of developing DM than HCV-negative patients (28.0% vs 6.2% at 10 years; P=001). In G1, multivariate analysis showed that age, BMI, and HCV-positivity were significant risk factors predicting DM (relative risk, 5.7; 95% confidence interval 2.7-12). In G2 patients, HCV was not associated with an increased risk of DM; in the multivariate analysis only age appeared to be a risk factor. CONCLUSIONS: The reported relationship between hepatitis C and post-RT DM was not observed among patients receiving new immunosuppressive treatments. Confirmation of this finding requires extended follow up. The reduced use of steroids and effective pre-RT use of interferon may also be responsible for the benefit.

Adult↗

Synergic activity of fluoroquinolones and linezolid against Mycobacterium tuberculosis.

We evaluated the in vitro activity against Mycobacterium tuberculosis of the combination of fluoroquinolones and linezolid with classical drugs. The combination of isoniazid with fluoroquinolones had synergic activity in nine of the ten isoniazid-susceptible strains. We also found synergism between rifampicin and linezolid in five of the 15 strains susceptible to rifampicin. The clinical significance of these findings should be evaluated.

Acetamides↗

In vitro activity of new fluoroquinolones and linezolid against non-tuberculous mycobacteria.

The objective of the study was to determine the activity of new fluoroquinolones and linezolid against 108 clinical isolates of different species of non-tuberculous mycobacteria isolated in Spain. Gatifloxacin and moxifloxacin were found to be more effective than levofloxacin. Mycobacterium kansasii was more susceptible to the fluoroquinolones tested than M. avium complex and M. fortuitum was more susceptible than M. chelonae. Linezolid was more active against M. kansasii than against M. avium complex. A better understanding of the relationship between the in vitro activity of these compounds and their usefulness in the treatment of these infections is needed. The new fluoroquinolones exhibit good activity against M. kansasii and M. fortuitum and linezolid is active against M. kansasii.

Acetamides↗

Gene promoter hypermethylation in oral rinses of leukoplakia patients--a diagnostic and/or prognostic tool?

Leukoplakia is the most frequent oral precancerous lesion and shows a variable rate of malignant transformation. We hypothesised that the detection of molecular alterations, like the promoter hypermethylation of DNA, in oral cytological samples from patients at risk of developing primary or recurrent tumours could be a valuable diagnostic and prognostic tool in the management of these lesions. Two groups of patients with differing risks of developing oral squamous cell carcinoma (OSCC) were analysed. DNA was extracted from the oral rinse of each patient. The methylation status of the p16, p14 and MGMT gene promoters was determined using a methylation-specific polymerase chain reaction (MSP). Methylation of p16 and MGMT was observed in 44 and 56% of the oral samples, respectively. Only 12% of the cases showed p14 methylation. DNA hypermethylation was more frequent in patients with previous OSCC. DNA promoter hypermethylation is frequent during early oral carcinogenesis and even more so in the later stages. MSP using oral rinses is a non-invasive and highly sensitive technique which could be used to monitor patients with precancerous and cancerous oral lesions.

Adult↗

Thermal inactivation of Enterococcus faecium: effect of growth temperature and physiological state of microbial cells.

AIMS: To provide data on the effects on culture temperature and physiological state of cells on heat resistance of Enterococcus faecium, which may be useful in establishing pasteurization procedures. METHODS AND RESULTS: The heat resistance of this Ent. faecium (ATCC 49624 strain) grown at different temperatures was monitored at various stages of growth. In all cases, the bacterial cells in the logarithmic phase of growth were more heat sensitive. For cells which had entered in the stationary phase, D70 values of 0.53 min at 5 degrees C, 0.74 min at 10 degrees C, 0.83 min at 20 degrees C, 0.79 min at 30 degrees C, 0.63 min at 37 degrees C, 0.48 min at 40 degrees C and 0.41 min at 45 degrees C were found. By extending the incubation times cells were more heat resistant as stationary phase progressed, although a different pattern was observed for cells grown at different temperatures. At the lower temperatures heat resistance increased progressively, reaching D70 values of 1.73 min for cells incubated at 5 degrees C for 50 days and 1.04 min for those grown at 10 degrees C for 16 days. At other temperatures assayed heat resistance became stable for late stationary phase cells, reaching D70 values of 1.05, 1.08 and 1.01 min for cultures incubated at 20, 30 and 37 degrees C. Heat resistance of cells obtained at higher temperatures, 40 and 45 degrees C, was significantly lower, with D70 values of 0.76 and 0.67 min, respectively. Neither the growth temperature nor the growth phase modified the z-values significantly. CONCLUSIONS: D70 values obtained for Ent. faecium (ATCC 49624) varies from 0.33 to 1.73 min as a function of culture temperature and physiological state of cells. However, z values calculated were not significantly influenced by these factors. A mean value of 4.50 +/- 0.39 degrees C was found. SIGNIFICANCE AND IMPACT OF THE STUDY: Overall results strongly suggest that, to establish heat processing conditions of pasteurized foods ensuring elimination of Ent. faecium, it is advisable to take into account the complex interaction of growth temperature and growth phase of cells acting on bacterial thermal resistance.

Colony Count, Microbial↗

Hypothalamic levels of NPY, MCH, and prepro-orexin mRNA during pregnancy and lactation in the rat: role of prolactin.

Pregnancy and lactation provide excellent models of physiological hyperphagia and hyperprolactinemia. To identify possible factors associated with the increased feeding in these situations, we measured hypothalamic mRNA levels of three orexigenic neuropeptides--NPY, MCH, and orexins--in nonpregnant, pregnant, and lactating rats by in situ hybridization. NPY mRNA content in the arcuate nucleus was significantly increased during pregnancy and lactation. However, MCH and prepro-orexin expression was decreased in both states. 48 or 72 h of fasting in pregnant and lactating rats further elevated NPY mRNA levels and increased the low MCH mRNA content. Surprisingly, no effect was observed in prepro-orexin mRNA levels. Finally, we investigated the possible effect of high PRL levels on these orexigenic signals using a model of hyperprolactinemia induced by pituitary graft. NPY mRNA content was unchanged, but MCH and prepro-orexin mRNA levels were significantly decreased. Our results suggest that the increased NPY expression might be partly responsible for the hyperphagia observed during pregnancy and lactation. MCH and prepro-orexin may be involved in the adaptation of other homeostatic mechanisms and their decreased levels in these physiological settings could be mediated by the elevated circulating PRL levels.

Animals↗

Association of MICA-A5.1 allele with susceptibility to celiac disease in a family study.

OBJECTIVE: The aim of this study was to analyze the role of the major histocompatibility complex class I chain-related gene A (MICA) transmembrane polymorphism in celiac disease (CD) susceptibility. METHODS: Sixty-one celiac Spanish families were genotyped for MICA transmembrane polymorphism by a polymerase chain reaction method combined with fluorescent technology. A transmission disequilibrium test was performed to investigate the preferential transmission of MICA alleles to the affected offspring. RESULTS: The MICA A5.1 allele was shown to be significantly transmitted to the affected siblings. This association was independent of the CD-predisposing DQ2 haplotype. Additionally, we classified our celiac families into typical and atypical groups as we found a significant association with MICA A5.1 in typical celiac families. There was also an association tendency with atypical families. CONCLUSIONS: Our data suggest that the MICA A5.1 allele is associated with CD development independently of DQ2-extended haplotype and clinical forms of CD.

Alleles↗

[Extensive aganglionosis. Treatment and long term results].

INTRODUCTION: Extensive aganglionosis (EA) that affects the total colon (including or not part of the small intestine), shows more diagnostic problems and it is associated to higher morbidity and mortality rates than the classic cases of Hirschsprung disease (ED). This study takes into account last years cases and their results in the medium and long term. MATERIAL AND METHODS: Between 1983 and 2000, 232 patients suffering ED have been treated. 15 out of those 232 patients showed EA. We took into consideration the diagnosis, surgical procedures, enterocolitis before and after the treatment, the surgical technique and the complications. We analyze the nutritional state and the long term result according to clinical bowel function scoring system continency Scale, considering the surgical possibilities depending on each case. RESULTS: Two patients died due to septics complications, one of them during the neonatal period and the other one at the age of 3. Two other cases became possible candidates to an intestinal transplantation due to the extension of their disease. Five out of the 11 left patients had more than 30 cm of small intestine involved, and another five had involved less than 30 cm from ileocecal valve. The last case showed a total colonic aganglionosis with associated intestinal neuronal displasia. One case was associated with S. Ondine and another one with a 21 triosomia. Two of the patients were brothers and another patient has got a brother suffering from rectosigmoid HD. The surgical techniques used with 13 were: 8 cases using Lester Martin modification (one of them needed redo procedure because of anastomosis leak and perineal fistula), 4 Swenson procedure and one patient was treated by Ziegler's miectomy with prolongated miotomy. Nine of the patients mentioned before, lead a quite life (five L, Martin, 4 Swenson); 2 patients suffering frequent fecal retention crisis. 5 out of the 11 reviewed cases, show a weight and height p > or = 50, 2 below p50, 2 below p25, and 2 under p3. CONCLUSION: EA represents a small percentage of Hirschsprung disease. Although Martin modification is the most widely employed technique in cases of distal ileal involvement, Swenson procedure has provided good results in the long term follow-up with few complications. Intestinal transplantation may be the only choice for long term survival in patients with near total intestinal aganglionosis. Continence improves in the follow-up but few times is normal. Nutritional state should be-controlled by a specialized team.

Child, Preschool↗

[Emmetropization at cataract surgery. Looking for the best IOL power calculation formula according to the eye length].

PURPOSE: To determine the predictability of different intraocular lens (IOL) power calculation formulas (SRK-II, Binkhorst-II, Hoffer Q, Holladay y SRK/T) according to the axial length (AL). METHOD: The residual refractive error for each formula was determined in 212 cases of phacoemulsification with IOL implantation and it was compared to the < > result (the ideal result was emmetropia in all cases). RESULTS: The refractive error obtained with all different formulas for the AL group between 22 and 28 mm was not statistically significant. The error between the AL group of <22 mm and the AL group between 22-28 mm was not statistically significant for Binkhorst-II and Hoffer Q formulas. The error between the AL group > 28 mm and the group between 22-28 mm was not statistically significant for SRK/T. CONCLUSION: For small eyes (<22 mm) the Binkhorst-II and Hoffer Q formulas provided the best predictive results, whereas in long eyes (>28 mm) the SRK/T is the most accurate.

Humans↗

Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker.

The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT-PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I matched melanoma lines. The potential of targeting melanocortin 1 receptor in therapy and diagnosis will depend on a preferential expression of this receptor in the majority of primary and metastatic melanomas vs normal tissues. We tested a panel of melanomas, carcinomas and other cell lines for the presence of melanocortin 1 receptor, using two monoclonal antibodies. The receptor was detected in 83% of the tested melanoma cell lines but not in other carcinoma lines. Immunohistochemistry revealed a strong expression of melanocortin 1 receptor in all tested primary and metastatic melanomas, but also demonstrated low levels of expression in adrenal medulla, cerebellum, liver and keratinocytes. Flow cytometry studies showed that melanocortin 1 receptor was expressed in in vitro activated monocytes/macrophages and in the THP-1 monocytic leukaemia line at levels of about 1 in 3 to 1 in 5 of that found in melanomas. Peripheral blood-derived dendritic cells, also express melanocortin 1 receptor in vitro. This extensive analysis of melanocortin 1 receptor tissue distribution may be of relevance not only for melanoma immunology, but also for research on the pathogenicity of inflammatory conditions in the skin and neurologic tissues. It remains to be seen if the over-expression of melanocortin 1 receptor in melanomas is sufficiently high to allow a 'therapeutic window' to be exploited in cancer immunotherapy.

Biomarkers, Tumor↗

In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against Mycobacterium tuberculosis.

The in vitro activity of moxifloxacin, gatifloxacin, levofloxacin and linezolid was evaluated against 234 strains of Mycobacterium tuberculosis isolated in the Southeast of Spain. All drugs tested showed good activity, with an MIC(90) of less than 1 mg/l, and were active against isociacide and rifampicin resistant strains. Three strains were resistant to isoniazid and to the fluoroquinolones, which suggested the existence of mechanisms of resistance not yet described. These new compounds may prove to be therapeutic alternatives for treatment of multi-resistant tuberculosis and further studies should be done to demonstrate their true usefulness.

Acetamides↗

Anaesthetic and postoperative analgesic effects of spinal clonidine as an additive to prilocaine in the transurethral resection of urinary bladder tumours.

BACKGROUND AND OBJECTIVE: The alpha 2-adrenoceptor agonist clonidine has potent central antinociceptive properties. The study was designed to investigate the effects of the combined subarachnoid administration of clonidine and prilocaine on spinal block and postoperative analgesia for the transurethral resection of tumours in the urinary bladder. METHODS: The controlled, prospective, double-blind study enrolled 40 patients scheduled for elective transurethral resection of bladder tumours under spinal anaesthesia with prilocaine. Patients were randomly assigned to receive an intrathecal injection of prilocaine 75 mg alone (control group) or in combination with clonidine 75 micrograms. We assessed haemodynamic changes (non-invasive arterial pressure, heart rate), pulse oximetry, the upper level of block, the onset and duration of sensory and motor block, postoperative analgesia and any adverse effects. RESULTS: There were no statistically significant differences in demographic data, heart rate, onset time or the levels of sensory or motor block. Analgesia lasted significantly longer in the clonidine group (498.4 +/- 226.9 versus 187.2 +/- 103.1 min; P < 0.05). The duration of motor block was longer in the clonidine group (165.5 +/- 30.6 min) than in the control group (139.7 +/- 40.4 min; P < 0.05) and the duration of sensory block was also longer in the clonidine group (157.3 +/- 24.5 min) than in the control group (137.2 +/- 31.2 min; P < 0.05). Fewer patients in the recovery room needed metamizol (dipyrone) in the clonidine group (5%) than in the control group (50%). Arterial pressure decreased significantly in the clonidine group 75-135 min after the block. CONCLUSIONS: The addition of clonidine 75 micrograms to prilocaine 75 mg for subarachnoid anaesthesia increased the duration of sensory and motor block and reduced the need for additional postoperative analgesics by providing excellent analgesia for about 8 h during recovery from transurethral resection of bladder tumours.

Aged↗

[Cost of maintenance immunosuppressive drugs in kidney transplantation].

METHOD: We calculated the cost of maintenance immunosuppression (ISM) in 405 kidney transplant patients under treatment for more than one year, classifying them according to the combination of drugs used and whether the ISM continued to be the same as initially indicated (primary ISM), or a later adaptation. Basic clinical data were also acquired on the through levels of drugs and the use and cost of the associated medication. RESULTS: The mean doses in mg/kg/day and the trough levels in ng/ml were: cyclosporin (Cs), 2.7 +/- 0.9 and 123 +/- 5; tacrolimus (T), 0.09 +/- 0.06 y 7.3 +/- 2.9; Mycophenolate mofetil (MMF), 21.6 +/- 6.8 and 3.3 +/- 2.4. The proportion of patients with doses of steroids (EST) below 5 mg/day among patients treated with MMF was 60% in association with Cs and 73% with T. The cost related to EST and azathioprine (AZA) is very low; the mean cost per patient and day for Cs, T and MMF, was 7.08, 12.59 and 9.53 euros, respectively. The annual cost per patient depending on treatment was, in euros: EST + AZA, 204; Cs or without AZA and/or EST: 2,555; T with or without AZA and/or EST: 4,616; Cs plus MMF with/without EST: 6,136; T plus MMF with/without EST: 7,212. In cases of primary ISM, the difference between the two treatments with MMF drops so, low that its loses statistical significance (7,206 and 6,443 euros). This is because the dose of MMF is 50% higher in cases treated with Cs, even though there is no difference in the trough level of MMF. The use of hypolipidemic agents (with a mean annual cost of 451 euros) is much lower in treatments with T in comparison with Cs (13.8% vs 41.4%, p < 0.001). No significant differences could be established between T and Cs regarding the use of hypotensive agents and the frequency of postransplant insulin dependent diabetes. CONCLUSIONS: The treatment of ISM with T is more expensive than Cs based treatment but the difference is reduced in combination with MMF because of the use of lower doses of MMF in the association of T with MMF. The considerable economic impact of ISM would justify the provision of greater resources to the rationalisation of the treatments currently being applied.

Costs and Cost Analysis↗

Endotoxin and anti-endotoxin antibodies in the prognosis of acute pancreatitis.

AIMS: We investigate the behaviour of endotoxin in patients with acute pancreatitis and its relationship with the development of complications. EXPERIMENTAL DESIGN: Prospective study. PATIENTS: We assessed plasmatic endotoxin and anti-core endotoxin antibodies (EndoCab IgG and IgM) levels on first and third days from admission in patients with acute pancreatitis episodes, classifying them as mild or severe according to Atlanta's criteria. RESULTS: Nineteen patients were included, seven with severe pancretitis (36.8%) and twelve with mild pancreatitis (63.2%). Endotoxin levels were similar on first day in both mild and severe pancreatitis, and higher in the latter on third day (p > 0.05). Patients with severe pancretitis had lower EndoCab IgM levels on first and third days from admission (day 1: 18.3 vs 33.3 MU/ml, p < 0.01; day 3: 18.4 vs 33.4 MU/ml, p < 0.05). When analysed separately systemic and local complications, we observed, in the same days, a decrease of EndoCab IgM levels in patients who developed systemic complications (day 1: 18.3 vs 32.7 MU/ml, p = 0.01; day 3: 18.3 vs 35.1 MU/ml, p < 0.01). EndoCab IgG levels were also lower in severe acute pancreatitis in both determinations, but differences weren't significant. CONCLUSIONS: EndoCab levels decrease early in severe acute pancreatitis, mainly if systemic complications are present. This antibody depletion is greater for IgM than IgG, and seems to occur earlier than an increase in endotoxemia.

Acute Disease↗

Increasing impact of chronic viral hepatitis on hospital admissions and mortality among HIV-infected patients.

To assess the impact of chronic viral liver disease (CVLD) on hospital admissions and death in HIV-infected patients since the introduction of highly active antiretroviral therapy, all hospital charts, from January 1996 to December 2000, in a large HIV/AIDS reference center in Madrid were reviewed. Discharge diagnosis, complications during the inpatient period, and number and causes of death were recorded. A total of 1334 hospital admissions involving 875 HIV-infected individuals was recorded. Up to 82% of them were either active or former intravenous drug users. Overall, 158 (11.8%) were admitted because of complications of CVLD, or developed complications of CVLD during their admission for another reason. The absolute number and proportion of admissions caused by CVLD increased over time, from 9.4% (31 of 330) in 1996 to 16% (46 of 287) in 2000 (p < 0.05). Likewise, the total number and proportion of deaths due to CVLD increased from 9.3% (5 of 54) in 1996 to 45% (9 of 20) in 2000 (p < 0.05). Chronic hepatitis C was the only etiology in nearly three-quarters of patients who were admitted or died of CVLD. In conclusion, the proportion of hospital admissions caused by liver failure in HIV-infected patients has increased in the last 5 years, accounting for 16% of cases in 2000. End-stage liver disease currently represents 45% of causes of in-hospital death among HIV-infected individuals. Therefore, strategies to prevent infection by hepatitis viruses (hepatitis B vaccine) and specific treatment (interferon plus ribavirin for hepatitis C virus) should be encouraged among HIV-infected persons.

Adult↗