Changing the debate about health research for development. International Health Research Awards Recipients.
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Awards and Prizes↗
Biomedical subjects
A López
Publications and source records attributed to A López.
Immunohistopathological findings in the lungs of calves naturally infected with Mycoplasma bovis.
Histology and immunohistochemistry were used to analyse the lesions and distribution of Mycoplasma bovis antigen in the lungs of 18 naturally infected calves. Microscopic examination of pneumonic lungs revealed two distinct patterns of necrosis and inflammation. The first pattern was observed in six of 18 (33.3%) calves in which microscopic lesions were characterized by large irregular areas of coagulative necrosis surrounded by a dense zone of degenerated neutrophils. Moderate amounts of mycoplasmal antigen were in the centre and periphery of these necrotic foci and, to a lesser extent, in mononuclear cells of the peribronchial lymphoid tissue. The second pattern was observed in 18 of 18 (100%) calves and consisted of rounded foci of caseous necrosis composed by granular eosinophilic material surrounded by a rim of granulation tissue. Large amounts of M. bovis antigen were detected in the centre and periphery of these necrotic foci and, to a lesser extent, in the peribronchial lymphoid tissue, and alveolar and interstitial macrophages. It was concluded that both caseous and coagulative necrosis of the lung parenchyma was primarily caused by M. bovis. Infection with M. bovis should be suspected in bovine necrotic bronchopneumonia, particularly in cases in which the pulmonary necrosis is part of a pyogranulomatous inflammation centred around airways. The pattern of caseous necrosis with pyogranulomatous inflammation is characteristic of M. bovis infection while the pattern of coagulative necrosis is similar to and must be differentiated from Mannheimia haemolytica and Haemophilus somnus infection.
Animals↗
Dura-arachnoid lesions produced by 22 gauge Quincke spinal needles during a lumbar puncture.
AIMS: The dural and arachnoid hole caused by lumbar puncture needles is a determining factor in triggering headaches. The aim of this study is to assess the dimensions and morphological features of the dura mater and arachnoids when they are punctured by a 22 gauge Quincke needle having its bevel either in the parallel or in the transverse position. METHODS: Fifty punctures were made with 22 gauge Quincke needles in the dural sac of four fresh cadavers using an "in vitro" model especially designed for this purpose. The punctures were performed by needles with bevels parallel or perpendicular to the spinal axis and studied under scanning electron microscopy. RESULTS: Thirty five of the 50 punctures done by Quincke needles (19 in the external surface and 16 in the internal) were used for evaluation. When the needle was inserted with its bevel parallel to the axis of the dural sac (17 of 35), the size of the dura-arachnoid lesion was 0.032 mm(2) in the epidural surface and 0.037 mm(2) in the subarachnoid surface of the dural sac. When the needle's bevel was perpendicular to the axis (18 of 35) the measurement of the lesion size was 0.042 mm(2) for the external surface and 0.033 mm(2) for the internal. There were no statistical significant differences between these results. CONCLUSIONS: It is believed that the reported lower frequency of postdural puncture headache when the needle is inserted parallel to the cord axis should be explained by some other factors besides the size of the dura-arachnoid injury.
Arachnoid↗
[Pulmonary hemorrhage and anti-phospholipid syndrome].
The presence of anti-phospholipid antibodies (anticardiolipin antibodies and lupus anticoagulant) associated to venous and/or arterial thrombotic phenomena and fetal losses define the anti-phospholipid syndrome. On rare occasions severe hypoprothrombinemia associated with this disease as a cause of hemorrhagic manifestations has been described. In addition very few cases of alveolar hemorrhage in anti-phospolipid syndrome (APS) have been described, being this complication usually related to microthrombosis and/or capillaritis of pulmonary vessels. We describe two patients without previous clinical manifestations of anti-phospholipid syndrome that showed pulmonary hemorrhage with anticardiolipin antibodies positivity. The first of them, a 33-year-old male, began his disease with low prothrombin time and the presence of antiprothrombin antibodies. In the biopsy by thoracoscopy the presence of pulmonary hemorrhage without capillaritis nor thrombotic phenomena was demonstrated, becoming evident certain clinical improvement and normalization of the prothrombin time after receiving immunosuppressive treatment but with persistence of the pulmonary hemorrhage 5 years later. The second case, a 89-year-old male, began his condition with bilateral lung infiltrates and hemoptysis, anticardiolipin antibodies positivity, and thrombopenia, with recurrence of the condition 1 year later. After other etiological possibilities were ruled out, and despite hemorrhagic trait in both patients, we consider that they should be in the clinical context of the anti-phospholipid syndrome, although at this time they did not meet the criteria recognized in order to diagnose this disease. Within the ampliable clinical spectrum of the anti-phospholipid syndrome we should take into account the pulmonary hemorrhage.
Adult↗
[Intracranial and spinal subdural hematoma: a rare complication of epidural and subarachnoid anesthesia].
Subdural and epidural hematomas complicating central blocks are rare but serious complications that can lead to permanent neurological deficits. This review discusses cranial and spinal subdural hematomas, including the history of this complication in the literature. Theories to explain the mechanisms by which hematomas are formed are presented and risk factors are analyzed. The associations between such hematomas and the design of the various needles used for lumbar puncture are evaluated and the most common cranial and spinal locations are discussed. The anatomy of tissues that envelop and contain chronic subdural hematomas are described and the various neurological alterations that can develop are mentioned. Finally, diagnostic imaging options and corrective surgical techniques are reviewed.
Anesthesia, Epidural↗
[Origin of spinal subdural hematomas: a postmortem anatomical study].
OBJECTIVE: Although the mechanism by which cranial subdural hematomas form is known, the formation of spinal subdural hematomas is less clearly defined. The aim of this study was to identify vessels that can be found in the dural sac and whose rupture might lead to the formation of spinal subdural hematomas. MATERIAL AND METHOD: The dura mater, subdural space, and the arachnoid mater were studied in samples of dural sac taken from the eleventh thoracic vertebra to the fifth lumbar vertebra. The samples were taken from 3 fresh cadavers. Some were fixed in glutaraldehyde, dehydrated, and metallized with gold for scanning electron microscopy. Others were fixed in glutaraldehyde, treated with osmium tetroxide, and embedded in an epoxy resin for observation under a transmission electron microscope. RESULTS: Small hematomas--some on the internal surface of the dura mater and others surrounding nerve roots--were found within a thin, translucent arachnoid mater. Vessels measuring up to 100 microm were found within the dura mater, between its inner and outer laminae. Venules and capillaries were observed in the subdural space and in the arachnoid mater. CONCLUSIONS: Vessels are present between the laminae of the dura mater, in the subdural space, the arachnoid mater, and in spinal nerve roots. The rupture of these vessels could account for the formation of spinal subdural hematomas.
Cadaver↗
[Modifications of the lipid metabolism induced by interferon beta in multiple sclerosis patients and its relationship with the disease activity].
INTRODUCTION: It has been recently suggested that total cholesterol and low density lipoproteins (LDL) levels can behave as biological markers of activity in demyelinating diseases. Thus, our aim has been to describe the modifications of the plasma levels of total cholesterol and triglyceride due to treatment with interferon-beta in multiple sclerosis (MS) patients and to determine their relationship with the disease activity. PATIENTS AND METHODS: Study of the follow-up of MS patients under treatment with interferon-beta. Clinical and analytical controls were performed before initiating treatment and than at 1, 3, 6, 12, 18 and 24 months of its initiation. RESULTS: Fifty six patients have been studied, 41 of them women. Mean age was 37.4 years. Fifty were relapsing- remitting forms and the rest secondary progressive forms. The mean plasma levels of triglyceride increased and total cholesterol levels diminished during the 24 months of treatment with interferon, mainly in the first 3 months. No statistically significant relationship was found between disease activity and mean plasma levels of triglyceride and total cholesterol before the beginning of the treatment and during the period of follow-up. CONCLUSIONS: Treatment with interferon-beta in the MS patients originates changes in the plasma lipid profile, but neither these changes nor the plasma lipid levels before the treatment behave as biological markers of disease activity.
Adjuvants, Immunologic↗
[Sleep disorders in multiple sclerosis].
INTRODUCTION: To determine the frequency of sleep disorders in multiple sclerosis (MS) patients and their relation with other manifestations of the disease. METHODS: Selected patients had clinically definite MS (relapsing-remitting and secondary progressive forms) and duration of the disease over two years. They were serially evaluated at the unit of demyelinating diseases of a third level hospital. The following scales were applied: the Pittsburgh Sleep Quality Index, the Hamilton Depression Rating Scale, EDSS, ISS and ESS. Statistical analysis by means of non parametric test and logistic regression was carried out. RESULTS: One hundred patients were included (72% women and 28% males). Mean age was 39 years. Eighty eight were relapsing-remitting forms and the rest secondary progressive forms. Mean EDSS was: 2.5. Mean duration of evolution: 11.2 years. The prevalence of sleep disorders was 36%. Age, sex, evolutionary form, degree of disability and chronic fatigue did not relate with the sleep disorders in these patients. In the multivariant analysis by means of logistic regression, we found that every point more in Hamilton's scale multiplies the probability of presenting sleep disorders by 1.2. CONCLUSIONS: Depression is the only variable that independently relates, with the presence of sleep disorders in MS patients.
Adolescent↗
Germline mutations at microsatellite loci in homozygous and heterozygous mutants for mismatch repair and PCNA genes in Drosophila.
Microsatellite instability (MSI) is a phenotype associated with the deficient repair of replication errors. Replication errors persist in defective mismatch repair (MMR) conditions, although alterations in components of the replication machinery, such as the proliferating cell nuclear antigen (PCNA) factor, could also increase the replication errors; therefore, MSI is expected in both situations. It also seems that heterozygous individuals for MMR genes have a high risk of cancer, as in the case of human non-polyposis colon carcinoma (HNPCC), characterised by MSI. Thus, here we investigate the effect of heterozygosity for a Msh2-null allele or for altered PCNA alleles, on the stability of microsatellite sequences. The study was carried out in Drosophila germ cells analysing the progeny of individual crosses. We found that one Msh2 disrupted allele is sufficient to produce MSI in germ cells. Although the MSI in Msh2(-/+) individuals was in the same order of magnitude as in Msh2(-/-) individuals, the former manifested a MSI that was four-fold lower. To a lesser extent, PCNA homozygous and heterozygous mutants also show MSI in the germline, which reveals the importance of DNA replication factors to maintain genomic stability in vivo. Furthermore, the high MSI found both in heterozygous Msh2 and PCNA mutants suggests a high degree of genomic instability in individuals bearing a mutant allele of these genes, which could have important implications in cancer susceptibility.
Animals↗
Intrinsic defects explain altered proliferative responses of T lymphocytes and HVS-derived T-cell lines in gastric adenocarcinoma.
We have taken advantage of a recently described technique of transformation and immortalization of T lymphocytes using the lymphotropic Herpesvirus saimiri, to achieve long-lasting T-cell lines from gastric cancer patients and healthy volunteers. Blood samples were drawn and T lymphocytes were transformed. Once sustained growth was observed, lines were subjected to phenotypic and functional analyses, and the results compared with freshly isolated peripheral blood mononuclear cells. Cytofluorometric analysis revealed that CD3 and CD45 were found at lower proportion in primary cells from patients than from control individuals (54% vs 75%, p<0.001, 90% vs 96%, p<0.05, respectively), and in HVS-derived T-cell lines (90% vs 98%, p<0.05, 97% vs 100%, p<0.05, respectively). Proliferative analyses showed that primary isolated cells were unable to respond adequately to CD3-, CD2-, and PHA-mediated stimulation, as compared to controls. Similarly, T-cell lines from patients proliferated to a lesser extent when CD3- and CD2-mediated stimuli were considered, especially when simultaneous stimulation via CD3 and CD2 molecules was carried out (47,824 counts per minute [cpm] vs 121,478 cpm, p<0.05). Altogether these results show that the defects reported in T cells from patients with cancer are not exclusively due to tumour-derived factors, since the alterations persist in long-lasting, HVS-transformed, T-cell lines, suggesting that this model seems a suitable one to disclose them.
Adenocarcinoma↗
[Value of C-reactive protein level in the detection of necrosis in acute pancreatitis].
OBJECTIVES: To evaluate the utility of C-reactive protein (CRP) in the detection of necrosis in acute pancreatitis and to determine the best cut-off point for CRP used for this purpose. MATERIAL AND METHODS: We performed a retrospective study of 157 patients with acute pancreatitis who underwent computed tomography (CT) with intravenous contrast material between 72 h and 8 days after the onset of symptoms and whose serum CRP values were determined by nephelometry 24 h or later after the onset of pain. RESULTS: Ninety-four patients were men and 63 were women, with a mean age of 61 years (range, 15-96 years). The cause of pancreatitis was biliary lithiasis in 53.5%, alcohol in 20.4%, and idiopathic in 10.8%. Other causes were found in 15.3%. The mean (standard deviation) time elapsed between symptom onset and extraction to evaluate CRP was 3.21 (1.7) days. The patients were divided into two groups according to the results of CT: 132 patients with acute intersitial edematous pancreatitis and 25 patients with acute necrotizing pancreatitis. The mean CRP concentrations were: 322 mg/l (range, 10.7-538) in patients with acute necrotizing pancreatitis and 133 mg/l (range, 3-442) in those with acute interstitial pancreatitis; this difference was statistically significant (p < 0.001). The area under the ROC curve of CRP vs. the occurrence of necrosis was 0.862 (95% CI, 0.778, 0.946). To evaluate the presence of pancreatic necrosis a cut-off level of 200 mg/l showed a sensitivity of 88% and a specificity of 75% while a cut-off level of 279 mg/l presented a sensitivity of 72% and a specificity of 88%. CONCLUSIONS: In acute pancreatitis, a CRP value of less than or equal to 200 mg/l obtained at 72 h of symptom onset is useful for ruling out, with a high degree of probability, the presence of necrosis. With higher values, additional investigations should be performed to determine the presence of pancreatic necrosis; nevertheless, with values higher than 279 mg/l the risk of necrosis markedly increases.
Acute Disease↗
[Chronic pancreatitis as the initial presentation of Crohn's disease].
It has been suggested that pancreatitis could be an extrahepatic manifestation of inflammatory bowel disease, since its incidence in this disease is greater than that in the general population and in many cases no etiological factor is found. We present a case of chronic idiopathic pancreatitis as the initial presentation of Crohn's disease of the colon.
Adult↗
[Gastroduodenal tuberculosis: a cause of pyloric stenosis].
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Aged↗
Validation and sensitivity analysis of a probabilistic model for dietary exposure assessment to pesticide residues with a Basque Country duplicate diet study.
The 'fitness for purpose' of a probabilistic model designed to assess dietary exposure to pesticides was validated. The model had to meet two prerequisites. First, it should provide more realistic estimates of intake than conservative methods. Second, it should not underestimate 'true' intakes. True intakes were estimated using a duplicate diet study. Three approaches were used to check the prerequisites: visual comparison, a statistical test of a high percentile, and a comparison for each infant of the duplicate diet, conservative and model intake values. Compliance with the prerequisites was met for the six pesticides selected, in the three approaches. Model outcome distributions reduced the uncertainty, considered as the difference between conservative and duplicate diet intakes, by 75-98% for high percentiles, depending on the pesticides. A sensitivity analysis of the model based on analysis of variance for selected factors was conducted for three pesticides. The factors included concentration and food consumption input data presentations, values assigned to pesticide-food commodities without analysis, values assigned to samples with results below the limit of reporting, unit-to-unit variability and processing factors. Their significance and relevance were studied. Assigning values to pesticide-food commodities without analysis and processing factors, when available, were the most relevant factors in this study.
Diet↗
Autologous stem cell transplantation for primary refractory Hodgkin's disease: results and clinical variables affecting outcome.
BACKGROUND: Patients with primary refractory Hodgkin's disease (PR-HD) have a dismal prognosis when treated with conventional salvage chemotherapy. We analyzed time to treatment failure (TTF), overall survival (OS) and clinical variables influencing the outcome in patients undergoing autologous stem cell transplantation (ASCT) for PR-HD and reported to the Grupo Español de Linfomas/Trasplante Autólogo de Médula Osea (GEL/TAMO). PATIENTS AND METHODS: Sixty-two patients, 41 males and 21 females with a median age of 27 years (range 13-55) were analyzed. Forty-two patients (68%) had advanced stage at diagnosis, 47 (76%) presented with B symptoms and 29 (47%) with a bulky mediastinal mass. Seventy-five percent of the patients had received more than one line of therapy before ASCT. Thirty-three patients received bone marrow as a source of hematopoietic progenitors, and 29 peripheral blood. Six patients were conditioned with high-dose chemotherapy plus total-body irradiation and 56 received chemotherapy-based protocols. RESULTS: One-year transplantation-related mortality was 14% [95% confidence interval (CI) 6% to 23%]. Response rate at 3 months after ASCT was 52% [complete remission in 21 patients (34%), partial remission in 11 patients (18%)]. Actuarial 5-year TTF and OS were 15% (95% CI 5% to 24%) and 26% (95% CI 13% to 39%), respectively. The presence of B symptoms at ASCT was the only adverse prognostic factor significantly influencing TTF [relative risk (RR) 1.75, 95% CI 0.92-3.35, P = 0.08]. The presence of B symptoms at diagnosis (RR 2.08, 95% CI 0.90-4.79, P = 0.08), MOPP-like regimens as first-line therapy (RR 3.84, 95% CI 1.69-9.09, P = 0.001), bulky disease at ASCT (RR 2.79, 95% CI 0.29-6.03, P = 0.009) and two or more lines of therapy before ASCT (RR 2.24, 95% CI 0.95-5.27, P = 0.06) adversely influenced OS. CONCLUSIONS: In our experience, although overall results of ASCT in PR-HD patients are poor, one-quarter of the patients remain alive at 5 years. Despite this, other therapeutic strategies should be investigated in this group of patients to improve the outcome.
Adolescent↗
[Epidural anesthesia with ropivacaine vs. bupivacaine in continuous perfusion for the treatment of labor pains].
OBJECTIVE: To compare the analgesic efficacy and extent of motor block when 0.125% ropivacaine or 0.125% bupivacaine were given in continuous perfusion through an epidural catheter during labor. PATIENTS AND METHODS: We studied 60 ASA I-II women, each carrying a single fetus at full term and in spontaneous labor. The patients were distributed in 2 groups. Women in the ropivacaine group (R) (n = 30) received 8 mL of 0.2% ropivacaine for analgesic induction, followed by a continuous perfusion of 10 mL/h at 0.125%. The bupivacaine group (B) (n = 30) received bupivacaine at the same concentration and infusion rate. The objective of analgesia was to achieve a score less than 3 on a visual analog pain scale. If analgesia was inadequate, a 5 mL bolus of 0.2% ropivacaine or bupivacaine, depending on group, was administered. The motor block was evaluated on an abbreviated Bromage scale and we recorded hemodynamic stability, fetal status, type of delivery and the total dose of local anesthetic. RESULTS: Analgesia and hemodynamics were similar in both groups. Group R required a larger number of additional boluses, although the difference was not statistically significant. A motor block was observed in 8 patients in group B and 1 in group R (p < 0.05). Fetal status was similar in both groups. CONCLUSION: Both drugs were equally effective for controlling the pain accompanying labor, such that ropivacaine offered no advantage over bupivacaine in that regard. Ropivacaine's reduced motor block effect at the doses administered may offer an advantage in some situations, such as when a walking epidural is provided.
Adrenergic Agents↗
[The blood-nerve barrier in peripheral nerves].
AIM: To study ultrastructural details of perineurium and endothelium samples from the endoneural vessels that form part of the blood-nerve barrier of peripheral nerves, with the intention of furthering our understanding of how these natural structures protect axons against foreign substances. METHODS: We obtained samples from the sciatic nerve at the superior angle of the popliteal fossa. The samples were first fixed in glutaraldehyde and then in osmium tetroxide; later they were dehydrated with acetone and soaked in resin epoxy (Epon 812). Ultra-thin sections were treated with uranyl acetate and lead citrate in solution. The slides were observed under a transmission electron microscope. RESULTS: The perineurium has a thickness of 10 to 25 microns and is composed of 8 to 15 continuous cell layers lying concentrically around each nerve fascicle. Each perineurial cell layer consists of a single layer of flat cells joined together by specialized junctions to provide a barrier against diffusion. Most of the endoneural vessels found near the axons were capillaries measuring 6 to 10 microns in diameter and composed of 6 to 8 endothelial cells with specialized junctions without fenestrations. CONCLUSIONS: The blood-nerve barrier is a cylindrical structure formed partly by membranes composed of tightly joined perineurial cell layers whose union is reinforced by specialized junctions that tend to isolate each fascicle. In addition, there is a cylindrical structure made up of endoneural endothelial cells also united by specialized junctures. These tend to keep blood away from axons and to impede the passage of circulating substances into the endoneural environment. Systemic diseases that alter and diminish the efficacy of the barrier in peripheral nerves may have implications for the creation of peripheral nerve blocks.
Aged↗
[Influence of early or late referral to nephrologist over morbidity and mortality in hemodialysis].
OBJECTIVE: We studied the influence of early vs late referral to nephrologist of patients with chronic renal failure over clinical situation at the onset of hemodialysis and outcome. SUBJECTS AND METHODS: From january 1994 to december 1998, 139 patients started hemodialysis for end-stage renal disease at the Hospital General de Albacete, all of them included in the study and clinical follow-up concluded in december 2001. Patients with rapidly progressive glomerulonephritis were excluded. Early (ER) and late referral (LR) were defined by the time of first nephrology encounter greater than or less than 6 months respectively, before iniciation of hemodialysis. RESULTS: 106 patients (76.25%) were referred early; mean follow-up time 6.3 +/- 4.5 years. 33 patients (23.74%) had late referral, follow-up time was less then six months, 18 patients were followed during less than 4 weeks. There were no differences in demographic data and comorbid conditions between LR and ER patients (age, cardiac and vascular disease, diabetes, neoplasia...). Mean plasma concentration of creatinine and urea was significantly greater, whereas hematocrit and albumin were less in the LRA than the ER group. Emergency dialysis through central vein catheterisation was more frequent in the LR group. Number of admissions and duration of hospital stay were higher in the LR group. No significant differences in nutrition, dialysis doses or anemia were found between the two groups after 6 and 12 months of hemodialysis. Long term outcome was similar in both groups: no significant differences were found in percentage of patients transplanted or deceased after 3 years of treatment. Survival analysis failed to show a difference between ER and LR groups (mean survival time was 73.6 +/- 4.3 months and 73.0 +/- 6 months respectively). CONCLUSION: Late referral to the nephrologist is associated with increased early morbidity vs early referral, although long term outcome is not worse if predialysis comorbid conditions are comparable and dialysis care achieve equal results in dialysis doses, nutrition and anemia in both groups in the first months of treatment. Improvement of outcome of patients referred early to the nephrologist will depend on the adoption of preventive measures over comorbidity factors that should be applied in early stages of renal disease.
Female↗