Biomedical subjects
Publications and source records attributed to M Martín.
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Opiate addiction is associated with abnormalities of neurofilament (NF) proteins and upregulation of cAMP signaling in the brain, which may modulate neuronal plasticity. This study investigated, using gene-targeted mice lacking mu-, delta- or kappa-opioid receptors, the role of these receptors in modulating the basal activity and the chronic effects of morphine on both intracellular targets. In WT mice, chronic treatment (5 days) with morphine (20-100 mg/kg) resulted in decreases in the immunodensity of neurofilament (NF)-L in the cerebral cortex (14-23%). In contrast, chronic morphine did not decrease NF-L in cortices of mu-, delta-, and kappa-KO mice, suggesting the involvement of the three types of opioid receptors in this effect of morphine. Also, the marked increase in phosphorylated NF-H induced by chronic morphine in WT mice (two-fold) was abolished in mu -KO mice. In cortex and/or striatum of mu-, delta- and kappa-KO mice, the basal immunodensities of Galphai1/2 proteins, the catalytic isoform (Calpha) of protein kinase A (PKA) and the total content of cAMP response element-binding protein (CREB, the nuclear target of PKA) were not different from those of WT mice. In contrast, phosphorylated CREB (the active form of this transcription factor) was reduced in cortex and/or striatum (23-26%) of mu- and delta-KO mice, but not in kappa-KO animals. These results suggest that the endogenous opioid tone acting on mu-/delta-receptors tonically stimulate CREB activation in the brain. In cortex and/or striatum of WT mice, chronic morphine did not induce upregulation of the main components of the cAMP signaling pathway. In contrast, chronic morphine treatment in mu-KO mice, but not in delta- or kappa-KO, resulted in a paradoxical upregulation of Galphai1/2 (12-19%), PKA (19-21%,) and phosphorylated CREB (21-73%), but not total CREB, in cortex and/or striatum. The induction of heterologous receptor adaptations in mu-KO mice may explain this paradoxical effect of morphine.
OBJECTIVE: To describe the characteristics of patients included in the pancreatic tumor registry of the Hospital Clínic of Barcelona. PATIENTS AND METHOD: All patients with pancreatic tumors attended between July 1990 and March 2003 were registered. Data collection included: age, gender, date of diagnosis, diagnosis, histology, size, location and tumor stage, and treatment. The correlation between tumor stage and age, date of diagnosis, and tumor location was also evaluated. RESULTS: Six hundred thirty patients with pancreatic tumors were included, representing an incidence of 60 patients/year. The mean age was 66 years and the male-to-female ratio was 1,18:1. The most frequent lesion was malignant tumor of the pancreas (92%), and the most frequent histological type was pancreatic ductal adenocarcinoma (73%). The most frequent location was the head of the pancreas (64%). In 28% of the patients, pancreatic cancer was diagnosed in stage I and II. Resection was performed in 31% of patients, whereas 48% of the patients received no treatment. The ratio between local (stage I)/disseminated (stage IV) disease was 0,34. The ratio between stage I/IV increased with age, diagnosis prior to 1994, and tumor location in the head of the pancreas. CONCLUSION: Hospital tumor registries can be used to define the profile of the attended population, which can help to delineate the best diagnostic-therapeutic strategy and can be useful in clinical research.
Several Aujeszky's disease virus (ADV) vaccination protocols of sows were evaluated with regard to the passive protection conferred on piglets in a recently built commercial farm. Three different groups of sows were vaccinated using a Bartha K-61 strain. One group received an inactivated vaccine during pregnancy and the other two groups received attenuated vaccines, either during pregnancy (day 65) or on the seventh day of lactation. At farrowing, sows vaccinated during lactation had lower seroneutralization titres than those vaccinated during pregnancy either with inactivated or attenuated vaccines. Accordingly, their piglets were the ones with lower levels of maternally transferred neutralizing antibodies. At 4 weeks of age, five piglets born of each group of sows were challenged intranasally with a neurotropic strain of ADV. Piglets born of sows vaccinated during pregnancy with inactivated and attenuated vaccines gained 1.50 kg bodyweight and 2.50 kg bodyweight during 7 days, respectively, and did not show clinical signs, while piglets from sows vaccinated during the previous lactation lost 0.60 kg and presented moderate to severe clinical signs of ADV. Vaccination of sows during pregnancy provided more protection against ADV for piglets than sow vaccination before mating. Piglets born from sows vaccinated with attenuated or inactivated vaccines did not present remarkable differences on protection.
INTRODUCTION: Atrial fibrillation is the most common arrhythmia on clinical practice and an important risk factor for ictus. The aim of this study was to know the prevalence of this arrythmia in a central district of Madrid. MATERIAL AND METHODS: A retrospective study was done analysing medical records of 13,945 patients belonging to a primary care centre of Madrid. Time of study: recruitment of data from September 2000 to May 2001; analysis of data: from September 2001 to May 2002. RESULTS: We obtained a total of 425 atrial fibrillations, 348 non-valvular and 77 valvular. Global prevalence of atrial fibrillation in patients over 40 years in our area was 2.52%. (2.47% male, 2.55% female). Risk factors for atrial fibrillation more frequently found in non-valvular were high blood pressure (HBP), diabetes, ischaemic heart disease and left ventricular dysfunction. Among valvulars we found HBP, left atrial size over 45 mm and left ventricular dysfunction. CONCLUSIONS: Atrial fibrillation shows a prevalence and distribution in the studied area similar to that found in other European countries.
PURPOSE: To determine if broken chromosome-end healing mechanisms through the addition of new telomeric sequences exist in cells having difficulties in rejoining the ends of broken chromosomes. MATERIALS AND METHODS: A full-colour painting protocol of all human chromosomes by FISH was combined with a telomeric and centromeric labelling using PNA probes to characterize the rejoining pattern and telomere status of radiation-induced chromosome breaks in ataxia-telangiectasia (A-T) and normal lymphoblastoid cell lines. RESULTS: It was first established that the cell lines used for chromosome healing analysis were chromosomally stable. FISH analysis provided evidence that the frequency of deleted chromosomes, apparently unrejoined, was much higher in A-T than in normal cells, as expected by the role of ATM in cell-cycle control, as well as in DNA repair. In spite of their high frequency, broken chromosome ends in A-T cells do not seem to act as substrates for telomerase since additional terminal telomere sequences (more than the 92 expected pairs) indicative of chromosome healing were never observed. Broken chromosome ends in A-T cells remained open. CONCLUSION: The disability of cells to rejoin broken chromosome ends does not lead to the healing of DSBs by the acquisition of new telomeric sequences.
Chronic R-N(6)-phenylisopropiladenosine (R-PIA) subcutaneous injection for 6 days significantly increased total glutamate receptor number (180% of control) in rat brain synaptic plasma membranes (SPM), without affecting receptor affinity. A higher increase in metabotropic glutamate (mGlu) receptor number (258% of control) was also detected, indicating that mGlu is the main type of glutamate receptor affected by this treatment. On the other hand, the observed increase in basal and calcium- and Gpp(NH)p-stimulated phospholipase C (PLC) activity after treatment was associated with a significant increase in PLC beta(1) isoform, detected in SPM by immunoblotting assays. Moreover, an increase in PLC activity stimulation with trans-ACPD, in the absence and in the presence of Gpp(NH)p, was detected after R-PIA treatment. These results show that mGlu receptors and its effector system, PLC activity, are up-regulated by chronic exposure to an adenosine A(1) receptor agonist and suggest the existence of a cross-talk mechanism between both signal transduction pathways in rat brain.
Klebsiella planticola strain DSZ1 has the ability to degrade different aromatic compounds such as benzoate and organochlorinated as propachlor and alachlor. DSZ1 strain cells mineralised 4-hydroxybenzoate (4HBA) through a meta-cleavage pathway, yielding protocatechuate as dihydroxylated intermediate, with a specific rate of CO2 formation 0.12 x 10-6 (cpm/OD) h-1, and a rate of 4-HBA utilisation of 0.75 mmol h-1. Aerobically the 4HBA transport system is driven by gradient of protons (DeltapH), but is not ATP-driven. Under anaerobic conditions, the system can use the nitrate reduction as a final electron acceptor in respiration. A kinetic analysis of the 4HBA transport system revealed a Kt value of 16 microM with a Vmax value of 25 nmol/min.mg at pH 7.
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INTRODUCTION: Because of the increased complexity of the diagnostic-therapeutic approach to colorectal cancer (CRC), these patients should be managed in specialized multidisciplinary units. The aim of this study was to evaluate the efficacy and efficiency of a CRC unit (CRCU) in the diagnostic-therapeutic management of these patients. PATIENTS AND METHODS: Two groups of 50 patients with colon cancer treated in our center before and after the implementation of the CRCU were selected. Fulfillment with the protocol in terms of tumoral staging, surgical and adjuvant treatment, follow-up, interval until treatment, hospital stay, morbidity and early mortality, and the overall duration of the diagnostic-therapeutic process was analyzed. In addition, clinical workload was evaluated and a cost-minimization analysis was performed. RESULTS: The CRCU reduced the interval until surgery (20.3 12.0 vs 28.0 20.4 days; p = 0.05), hospital stay (9.8 7.7 vs 14.5 9.3 days: p = 0.01), the time to the start of adjuvant treatment (29.4 10.2 vs 39.7 19.8 days; p = 0.03) and the overall duration of the process (60.4 23,8 vs 82.1 46.1 days; p = 0.05), representing a saving of 978.85 E per patient. This improvement took place despite an increase in clinical workload (24% in 5 years in relation to the number of admissions) and had no effect on morbidity (26 vs 24%; NS) or immediate mortality (6 vs 4%; NS). CONCLUSION: Specialized multidisciplinary units increase the efficacy and efficiency of the management of patients with CRC.
BACKGROUND: The aim of our study was to analyse patient characteristics, mortality and costs, all of them in relation to whether starting dialysis was planned or unplanned. METHODS: A total of 362 patients (227 male and 135 female) from five hospitals of the National Health System, who were started on chronic renal replacement therapy (RRT) during 1996 and 1997 were included. Patients who were started on RRT after acute renal failure were excluded. We carried out a retrospective analysis of the demographic characteristics, patients' conditions at the time of initiating dialysis and outcome and costs at six and thirty-six months of treatment. Patients were classified as planned (PL-D) or unplanned dialysis (UNPL-D), depending on whether or not the patient had a vascular or peritoneal access ready to use for initiating RRT. RESULTS: One hundred and eighty-six patients (51.4%) started on dialysis in the PL-D group whereas 176 (48.6%) did it as UNPL-D. In this latter group, 135 (37.3% of the total) had previously been monitored by a nephrologist, and 41 (11.3%) initiated dialysis without previous nephrological follow-up. UNPL-D was associated with older age (p < 0.001), non-nephrological follow-up (p < 0.001), diabetes (34.7% vs 22.6%) (p = 0.011), haemodialysis as a first mode of RRT (94.9 vs 81.7%) (p < 0.001), higher comorbidity risk (p < 0.001), dialysis initiation with uraemic symptoms or fluid overload (p < 0.001), increased blood transfusion requirement (p < 0.001) and lower serum albumin (p < 0.001), creatinine clearance (p < 0.001), haemoglobin concentration (p < 0.001), and weight (p = 0.002). In the PL-D group the main primary renal diseases were glomerular and polycystic disease, whereas interstitial and diabetic nephropathy were higher in UNPL-D group (p = 0.005). Multivariate analysis showed that previous non nephrological follow-up, uraemic symptoms, interstitial nephritis as primary renal disease correlated with UNPL-D initiation, and it was followed by choosing haemodialysis as first RRT. UNPL-D was also associated with increased number of days of hospitalization at the initiation of dialysis, and during the first 6 months (p < 0.001), increase of hospitalization days (p = 0.009), and increased 6-month-mortality (10.2% vs 3.2%) (p = 0.015, log rank test), and three-year mortality (24.2 vs 36.9%) (p = 0.006, log rank test). The costs of UNPL-D were fivefold that of the PL-D group. CONCLUSION: UNPL-D has been associated with worse overall clinical conditions at the initiation of chronic replacement therapy, choosing haemodialysis as first RRT, increased morbi-mortality and subsequent increase of costs.
BACKGROUND: Circadian rhythms shift out of phase after transmeridian flights. Desynchronization between body rhythms and the environment is linked to jet lag, which depends on age, flight direction, and number of time zones crossed. METHODS: To investigate this problem in airline pilots, we performed a multivariate analysis of their circadian systems during Madrid-Mexico-Madrid flights (-7 time zones, n = 12) and Madrid-Tokyo-Madrid flights (+8 time zones, n = 21). Telemetry was used to record pilots' activity, skin temperature, and heart rate, obtaining 6 d of continuous data, including 2 d before the flight, the flights themselves, 2 d at the stopover, and 1 d after the return flight. Time series were analyzed by cosinor, and the resulting parameters of the rhythms were compared by ANOVA and Tukey contrasts in every category formed by the age groups (under and over 50 yr old) and flight direction groups. Subjective time estimation of short, intermediate, and long intervals was recorded. Other psychological variables were measured, including anxiety, tiredness, and performance. RESULTS AND CONCLUSIONS: Activity/rest and heart rate rhythms appeared to be linked to a "weak oscillator." Temperature rhythms manifested a rigid response after the phase shifts of the light/dark cycle, closely related to the biological clock. Subjective time appreciation tended to be overestimated without exhibiting a clear circadian component, but attributable to fatigue and stress. Psychometric evaluation showed that desynchronization affected all the pilots. Some results showed an age-related variability with a more marked influence in younger pilots. No consistent effects regarding flight direction were found.
Porphyria cutanea tarda is treated with phlebotomies in the absence of renal failure. However, in patients on maintenance hemodialysis, this will lead to the need for high doses of erythropoietin. We describe the case of a 63-year-old hemodialysis patient who had chronic hepatitis C virus and developed porphyria cutanea tarda after iron overload due to repeated transfusions. She was treated with erythropoietin and phlebotomies reaching clinical remission 4 months after beginning treatment.
A study was carried out to compare the use of prophylactic imipenem administered at the onset of profound neutropenia (immediate) with therapeutic imipenem administered at the onset of neutropenic fever (delayed) in cancer patients treated with high-dose chemotherapy. A total of 65 patients who were scheduled to receive two cycles of high-dose cyclophosphamide, etoposide, cisplatin (CEP) chemotherapy were randomized to receive imipenem either at presentation of neutropenia (immediate imipenem arm, prophylactic arm) or at commencement of neutropenic fever (delayed imipenem arm, therapeutic arm). Treatment was crossed over when the second CEP chemotherapy cycle was received. Of the 65 patients, 41 received the two planned cycles and 24 received only the first. Compared with the delayed imipenem arm, the immediate imipenem arm was associated with lower fever incidence (86.3% vs. 100%, p=0.0142) and Gram-negative bacteria infection [4/51 (7.8%) vs. 14/55 (25.5%), OR=0.24, p =0.031]. There were fewer episodes of pneumonia (2% vs. 12.7%), septic shock (0% vs. 3.6%) and deaths from infection (0% vs. 3.6%), but these differences did not reach statistical significance. With regard to delayed imipenem, for every seven patients with immediate imipenem, one episode of febrile neutropenia was avoided; for every six patients administered immediate imipenem, one case of Gram-negative infection was avoided; and for every nine patients administered immediate imipenem, one episode of pneumonia was avoided. There were no differences in the incidence of Gram-positive infections nor in the length of hospitalization between the two treatment arms. In conclusion, compared to its conventional delayed use, immediate imipenem significantly reduces the frequency of febrile neutropenia and Gram-negative infections in patients with high-dose chemotherapy.
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X-linked lymphoproliferative disease (XLP) is a rare immune disorder commonly triggered by infection with Epstein-Barr virus. Major disease manifestations include fatal acute infectious mononucleosis, B-cell lymphoma, and progressive dys-gammaglobulinemia. SAP/SH2D1A, the product of the gene mutated in XLP, is a small protein that comprises a single SH2 domain and a short tail of 26 amino acids. SAP binds to a specific motif in the cytoplasmic tails of the cell surface receptors SLAM and 2B4, where it blocks recruitment of the phosphatase SHP-2. Here it is reported that Ly-9 and CD84, 2 related glycoproteins differentially expressed on hematopoietic cells, also recruit SAP. Interactions between SAP and Ly-9 or CD84 were analyzed using a novel yeast 2-hybrid system, by COS cell transfections and in lymphoid cells. Recruitment of SAP is most efficient when the specific tyrosine residues in the cytoplasmic tails of Ly-9 or CD84 are phosphorylated. It is concluded that in activated T cells, the SAP protein binds to and regulates signal transduction events initiated through the engagement of SLAM, 2B4, CD84, and Ly-9. This suggests that combinations of dysfunctional signaling pathways initiated by these 4 cell surface receptors may cause the complex phenotypes of XLP. (Blood. 2001;97:3867-3874)
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Although several reports have attributed the clinical benefits of highly active antiretroviral therapy (HAART) to a possible immune restoration, long-term data are still scarce and most derive from patients with either advanced or very early stages of HIV infection. In the present study, changes in lymphocyte subsets, activation markers, and adhesion molecules in CD4+ and CD8+ lymphocytes were carefully monitored over a 1-year period in 27 HIV-infected adults at an intermediate stage of HIV infection. Cytokine-producing patterns were also studied. In these patients the HIV viral load disappeared by month 4 of HAART. Only limited immunological changes were observed: an incomplete recovery of naive CD4+ T cells, a less activated state of CD8+ T cells, and a repopulation of IL-2- and IFN-gamma-producing CD4+ T cells. These changes were observed principally in patients with more advanced disease. Furthermore, HIV-infected subjects who had received HAART previously showed less marked immunological changes than antiretroviral-naive individuals. In conclusion, the sustained viral suppression during 1 year of HAART was accompanied by limited immunological recovery at intermediate stages of HIV infection. This finding indicates a need for longer HIV suppression in order to achieve effective recovery of the immune system.