Biomedical subjects
Publications and source records attributed to M Romero.
At the end of the 19th and beginning of the 20th centuries, a movement which proposed that dental check-ups and treatment be carried out among school children appeared world wide. In Spain, the leading representatives of this movement were Perez Cano and Otaola. Pressure from odontologists forced the government to promulgate two decrees which made dental check-ups obligatory for school children.
Coronary lesions located in major bifurcations constitute a challenge for the use of stents. Although the occlusion of a side branch covered by a stent is infrequent, the maintenance of a patent, stenosis-free bifurcation may result in a complex procedure. Between September 1994 and April 1998, 70 patients were treated by stent implantation for coronary bifurcation stenosis. The side branch always had a diameter >2 mm. The pairs of treated arteries were: left anterior descending (LAD)/diagonal artery in 32 patients, circumflex/obtuse marginal in 26, right coronary/posterior descending artery in 5, and LAD/circumflex in 7. We applied 2 different techniques of stent implantation: (1) deployment of 1 stent in the parent vessel covering the takeoff of the side branch and subsequent angioplasty of the side branch across the metallic structure (group A, n = 47 patients), and (2) implantation of 1 stent at the ostium of the side branch and complete reconstruction of the entire bifurcation with additional implantation of 1 or 2 stents at the parent vessel (group B, n = 23 patients). There were no significant differences between groups at baseline variables. Procedural success was similar in both groups: 42 (89%) in group A versus 21 (91%) in group B. However, major cardiac events at 18 months follow-up were higher in group B (event-free probability 44% vs 75%, p <0.05). Selected patients with coronary stenosis at major bifurcations can be treated with an acceptable rate of primary and late success. Complex techniques providing radical stent reconstruction of the bifurcation seems to provide no advantages over the simpler stent jail followed by ostial side branch balloon dilation.
Experimental studies have shown that stents implanted at the aorta become incorporated within the aortic wall and can be further expanded in growing animals. Few clinical studies have shown that the stent repair of severe coarctation of aorta provides excellent initial results, and little is known on the follow-up of these patients. We assessed the immediate and follow-up results obtained in a series of 48 patients (mean age 14+/-12 years) with severe coarctation of the aorta who were treated by Palmaz stent implantation; 30 of them (63%) underwent angiographic follow-up studies at a mean of 25+/-11 months after treatment. Quantitative serial analysis of the aortogram (baseline, after treatment, and at follow-up) was performed. Significant relief (mean residual gradient 3+/-4 mm Hg) was always obtained after stent implantation. The isthmus, when hypoplastic (60%), was always expanded with the stent. One associated aneurysm became occluded after the implant. Complications included aortic disruption, stent migration, and decreased or absent femoral pulses. At angiographic follow-up, the stent remained always in place, without recoil. In 22 patients (73%), there were no detectable neointimal proliferation at late angiogram; however, 8 patients (27%) had some degree of intimal thickening (1 to 5 mm), causing mild restenosis in 3 patients treated at early age, and nonsignificant lumen reduction in 5. The serial aortogram analysis revealed a minor but significant increase in nonstented aortic diameters that seemed related to the normal growth of children. No need for stent reexpansion was observed at 2-year follow-up (mean). Two patients (7%) developed late small aneurysm formation at the stented wall; both were occluded by the insertion of coils through the stent orifices. We conclude that stent treatment for severe coarctation of aorta provides excellent immediate and long-term results in young adults and children. However, at early age, restenosis by intimal growth may develop.
BACKGROUND: There is conclusive evidence from large scale randomized clinical trials (RCTs) that several treatments administered in the acute phase of a myocardial infarction (AMI) reduce mortality. However, only a minority of patients admitted with AMI receives at the appropriate treatments. OBJECTIVES: This study aims at (1) describe the utilization patterns for AMI; (2) determine the appropriateness of prescribing, measured as adherence to the ACC/ AHA guidelines; and (3) determine which factors are associated with the administration of thrombolytic agents. METHODS: The study was a multi-center survey carried out in ten countries (nine European and one Canadian province) over a 3-month period. Data were prospectively collected by clinical pharmacists. All consecutive patients admitted to the participating hospitals during the study period with a diagnosis of suspected AMI were included in the study. Rates of use were calculated as "overall utilization" and "adjusted utilization" (e.g., accounting for eligibility). RESULTS: Data were available on 1976 patients from 56 participating centers. The mean age of the patients was 65 years (range 25 95, SD = 12.6) and 29.7% were women. Adjusted utilization rates were 63.7% for thrombolysis, 88% for aspirin, and 65.9% for beta-adrenergic blocking agents. The most utilized thrombolytic agent was streptokinase (65.9%). The main reasons given by physicians for not administering thrombolysis was the delay from chest pain onset to admission. Patients admitted to teaching hospitals were less likely to receive aspirin than patients admitted to general hospitals (adjusted rate 90.1% vs 86%, P = 0.007), but they were more likely to undergo a primary invasive procedure (11.0% vs 2.5% P = 0.001). Multivariate analysis showed that age greater than 74 years, delay, prior myocardial infarction, and Killip scale were correlated with the non-utilization of thrombolysis. CONCLUSION: Recommended treatments are still under-utilized in patients with AMI. Increased utilization is required, particularly for elderly people. There is a wide variability among hospitals with different affiliations (teaching vs non teaching), demonstrating the different patterns of practice in various settings.
A monospecific Bothrops lanceolatus antivenom, currently used in Martinique, was tested for its efficacy in the neutralization of several toxic and enzymatic activities of the venoms of B. lanceolatus, B. atrox and B. asper. When tested by the i.p. route in mice, B. lanceolatus venom had an LD50 of 12.8 microg/g. In addition, it induced local tissue damage (hemorrhage, edema and myotoxicity) and showed indirect hemolytic activity, but was devoid of coagulant effect on human plasma in vitro and of defibrinating activity in mice. Antivenom was fully effective in the neutralization of lethal, hemorrhagic, edema-forming, myotoxic and indirect hemolytic effects of B. lanceolatus venom in assays involving preincubation of venom and antivenom. When tested against the venoms of B. asper and B. atrox, the antivenom completely neutralized the lethal, hemorrhagic, myotoxic and indirect hemolytic effects, and was partially effective in neutralizing edema-forming activity. In contrast, the antivenom was ineffective in the neutralization of in vitro coagulant and in vivo defibrinating effects induced by these two venoms.
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BACKGROUND/AIM: Ebrotidine is a new H2-receptor antagonist marketed in Spain in early 1997 and withdrawn in July 1998. We report 11 cases of acute liver injury related to ebrotidine and submitted to a Regional Registry of Hepatotoxicity between June 1997 and August 1998. METHODS: In all cases a structured protocol was used to ascertain the role of ebrotidine and to exclude other causes (viral, immunologic, metabolic) of liver injury. RESULTS: All patients showed clinical symptoms of acute hepatitis, with a marked increase in aminotransferase activities (ALT values ranging from 15 to 91 times the upper limit of normal). Total bilirubin values were also greatly increased (mean 16 mg/dl), and the liver injury was defined as hepatocellular. Features of hypersensitivity were absent. Liver biopsy was done in three patients. Histopathological examination revealed mainly centrozonal necrosis (two cases) or massive necrosis (one patient). Withdrawal of the drug was followed by a gradual improvement in liver dysfunction, except in one patient who developed fulminant hepatic failure and died. There was a positive response to rechallenge in one patient after an inadvertent drug administration. CONCLUSION: Ebrotidine therapy seems to be associated with severe acute liver injury, and therefore its benefit/risk ratio is unfavorable. The relative rareness and unpredictability of the injury, the lack of dose-relationship and the absence of hallmarks of drug allergy are suggestive of an idiosyncratic metabolic mechanism.
Steady state protein modification by carbonyl compounds is related to the rate of carbonyl adduct formation and the half-life of the protein. Thyroid hormones are physiologic modulators of both tissue oxidative stress and protein degradation. The levels of the glycation product N(epsilon)-fructoselysine (FL) and those of the oxidation products, N(epsilon)-(carboxymethyl)lysine (CML) and malondialdehyde-lysine (MDA-lys), identified by GC/MS in liver proteins, decreased significantly in hyperthyroid rats, as well as (less acutely) in hypothyroid animals. Immunoblotting of liver proteins for advanced glycation end-products (AGE) is in agreement with the results obtained by GC/MS. Cytosolic proteolytic activity against carboxymethylated foreign proteins measured in vitro was significantly increased in hypo- and hyperthyroidism. Oxidative damage to DNA, estimated as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8oxodG), did not show significant differences between groups. The results suggests that the steady state levels of these markers depend on the levels of thyroid hormones, presumably through their combined effects on the rates of protein degradation and oxidative stress, whereas DNA is more protected from oxidative damage.
BACKGROUND: Leukocyte infiltration is a common feature in renal biopsies from patients with acute poststreptococcal glomerulonephritis (APSGN). Cationic streptococcal erythrogenic toxin type B (ETB) and its precursor (ETBP) have been implicated in the pathogenesis of the disease, and the presence of ETB has been evidenced in renal biopsies from patients with APSGN. The present studies were performed to determine the effect of the ETBP and ETB on renal leukocyte infiltration and the mechanism(s) implicated in the phenomenon. METHODS: Male Sprague-Dawley rats were injected intrarenally with 100 microg of ETB or ETBP. Animals were sacrificed at 1, 6 and 24 h after injection and renal samples were studied by indirect immunofluorescence for the presence of leukocyte common antigen (LCA+) cells, C3, monocyte chemotactic protein-1 (MCP-1) and intercellular adhesion molecule-(ICAM-1), and by direct immunofluorescence for the presence of immunoglobulins. ETB and ETBP were tested for chemotactic effect and migration inhibition factor (MIF) activity by chemotaxis under agarose and agarose microdroplet methods, respectively. Streptococcal proteins were also tested for the capacity to induce MIF activity in rat glomerular cultures. To test for the influence of cationic charge on renal LCA+ cell infiltration, rats were injected with cationized ferritin or polyethyleneimine (PEI) and sacrificed 1 h later. RESULTS: An increased number of LCA+ cells was found in glomeruli and interstitial areas in ETB- or ETBP-injected animals. ETB and ETBP showed chemotactic and MIF activity on neutrophils and macrophages, and ETBP induced MIF activity in supernatants of glomerular cultures. Data obtained from C3, MCP-1, ICAM-1 or immunoglobulin renal staining in experimental animals were not significantly different when compared to control values. Cationized compounds failed to induce LCA+ cell infiltration; however, an increased number of glomerular LCA+ cells was observed after PEI perfusion. CONCLUSIONS: ETB and ETBP induce renal LCA+ cell infiltration during a short period after intrarenal injection, and this finding could be mediated by chemotactic and MIF activities. These observations could be relevant in the early events of pathogenesis of APSGN.
BACKGROUND AND OBJECTIVE: Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. DESIGN AND METHODS: A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb <= 100 g/L or receiving transfusions and serum erythropoietin <= 250 U/L. These patients were treated with subcutaneous rHuEpo (300 U/kg) three times a week for 8 weeks. In the case of partial response (PR) or no response (NR) subcutaneosly administered G-CSF (1 microg/kg) three times a week was added to the rHuEpo for 8 more weeks. If the patient achieved complete response (CR) or PR in the second phase, he was included in a follow-up phase of 24 weeks in which the dose of growth factors was tapered down. Several variables, including the score published by the Scandinavian-American group, were used as possible predictive variables. RESULTS: An erythroid response was observed in 16 patients (50%); in 12 it was a CR and in 4 it was a PR. During the period of rHuEpo administration, 7 CR and 4 PR (34.4%) were documented. Of the 14 patients in whom G-CSF was added to rHuEpo, 7 (50%) responded (3 CR and 4 PR). No major side-effects associated with growth factors were observed. The multivariate analysis showed that of the different variables evaluated only the Scandinavian-American response score was significant with a relative probability of response of 11.8 (95% confident intervals: 2.5-53) when this score was > +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. INTERPRETATION AND CONCLUSIONS: Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.
Liver biopsy after hepatic transplantation essential for the correct diagnosis of grant dysfunction. However, seriously imparied coagulation or massive ascites contraindicate percutaneous liver biopsy. In these cases transjugular liver biopsy may be valid alternative. in this study the efficacy, feasibility and safety of 69 transjugular biopsies carried out in 56 liver transplant recipients are evaluated. The suprahepatic veins were catheterized in 100% of the patients and histological samples were obtained in 63 (91.3%). The number of portal tracts was greater than six in 20.6% of the samples, lower than three in 35% and oscillated between four and six in 44%. The specimens obtained were sufficient for diagnosis in 82.5% of the patients, the overall diagnostic efficacy being 75.4%. The most common histological diagnosis (28.8%) was graft damage, while rejection represented 7.7%. Only one patient (1.18%) suffered a serious complication after transjugular biopsy. Transjugular biopsy is feasible and effective in liver transplant recipients with severely imparied coagulation.
Organic extracts representing 48 species included in 30 families of Costa Rican tropical plants were evaluated for their ability to neutralize hemorrhagic activity induced by the venom of the snake Bothrops asper. A bioassay in mice was used, based on intradermal injection of either venom or venom-extract mixtures followed by the measurement of hemorrhagic areas. Total inhibition of hemorrhage was observed with the ethanolic, ethyl acetate and aqueous extracts of Bursera simaruba, Clusia torresii, C. palmana, Croton draco, Persea americana, Phoebe brenesii, Pimenta dioica, Sapindus saponaria, Smilax cuculmeca and Virola koschnyi. Chemical analysis of these extracts identified catequines, flavones, anthocyanines and condensated tannins, which may be responsible for the inhibitory effect observed, probably owing to the chelation of the zinc required for the catalytic activity of venom's hemorrhagic metalloproteinases.
This chapter presents research findings from a collaborative project between Mexican investigators from the Mexican Institute of Psychiatry and the World Health Organization on the identification and treatment of harmful and hazardous drinking. A sample of 189 individuals who met criteria for hazardous drinking was selected for the study after screening 2319 outpatients attending clinics in two general hospitals in Mexico City. We present here the characteristics of this sample along dimensions that include alcohol related problems, history of trauma, alcohol dependence scores and family history of alcoholism. We rated, utilizing structures interviews, situations that place these individuals at risk of drinking. The possibility of constructing a typology of harmful and hazardous drinking was also explored. The significance of the findings of this investigation for health care clinicians is discussed.
Pulmonary complications after orthotopic liver transplant (OLT) are frequent, involving high morbidity and mortality. We have determined the pulmonary complication incidence in 187 patients submitted to OLT at the General University Hospital "Gregorio Marañón" in the last 4 years, analyzing the type of infection, evolution, diagnostic and therapeutic measures and their influence on OLT mortality. A total of 120 patients had pulmonary complications, the most frequent being pleural effusion (61.94%), pneumonia (43.36%), and pneumothorax (11.5%). Serious pulmonary hypertension was diagnosed by invasive methods in two patients at the time of surgery (unidentified before OLT); both died at early post postoperative times. Pleural effusion was noted in 70 patients, 31.42% of them requiring thoracic tube drainage, complications developing in 22.72%. Thirteen patients were diagnosed of pneumothorax, the most frequent etiologies being percutaneous liver biopsy, thoracic tube drainage for pleural effusion, and postoperative complications in 41.6, 33.3, and 23.3%, respectively. Pneumonia was diagnosed in the 1st month after OLT in 45 patients. Tests to diagnose and identify the etiological agent were made in 71.1% of diagnosed pneumonia patients, identification being obtained in 62.5%. Telescope catheter culture identified the agent in 48%, fiber optic bronchoscopy in 50%, and lung or pleural biopsy in 100%. Respiratory insufficiency was noted in 64 patients (34.22% of transplanted patients). Factors involved in their development were pneumonia (42.18%), graft dysfunction (39.06%, pleural effusion (34.37%), sepsis (28.18%), and poor nutritional status (7.81%). Fifty patients (41.66%) died, pulmonary pathology being the determinant factor in 28.8%. Patient mortality with respiratory insufficiency was greater, especially in those with three factors involved the development of respiratory insufficiency.
A comparative study was performed on the pharmacology and biochemistry of venoms from three subspecies of Lachesis muta (L. m. stenophrys, L. m. muta and L. m. rhombeata) from Brazil, Colombia and Costa Rica. All venoms induced lethal, hemorrhagic, edema-forming, myotoxic, coagulant and defibrinating effects, showing also proteolytic and indirect hemolytic activities. The venoms of L. m. stenophrys from Costa Rica and L. m. muta from Cascalheira, Brazil, had the highest lethal and hemorrhagic activities and the venom of L. m. rhombeata showed the highest coagulant activity, whereas no significant differences were observed in myotoxic and edema-forming activities at most of the time intervals studied. In addition, venoms showed similar electrophoretic patterns on SDS-polyacrylamide gel electrophoresis. In conclusion, despite quantitative differences in toxic and enzymatic activities, together with subtle variations in electrophoretic patterns, our results indicate that experimental envenomation by these venoms induce a qualitatively similar pathophysiological profile.
In this paper, we describe the conceptual bases and methodology used to assess women's and providers' perception of the quality of antenatal care, as part of a large randomised trial in four developing countries. Information has been obtained by applying both qualitative and quantitative methodologies. The focus group discussions and in-depth interviews have contributed useful insights into the cultural milieu in which care is provided, users' and providers' expectations, and their concept of quality. Based on these findings, we developed two standardised questionnaires, one being administered to a representative sample of pregnant women (n = 1600) and the other for all care providers. In this paper we present some of the findings of the focus group discussions and in-depth interviews with women in one country as an example of the kind of information we have obtained. Women expressed their point of view concerning a reduced number of visits, type of provider, information that they get during clinical encounters and interpersonal relations with health professionals. The qualitative information, together with the data we obtain from the surveys, will highlight the aspects that will have be to considered if the new model of care is to be introduced on a routine basis.
Paracoccidioidomycosis (PCM) is one of the most important endemic mycoses in Latin America; it is usually diagnosed by observation and/or isolation of the etiologic agent, Paracoccidioides brasiliensis, as well as by a variety of immunological methods. Although the latter are effective, two circumstances, cross-reactions with other mycotic agents and antigen preparation that is marked by extreme variability among lots, hinder proper standardization of the procedures. To circumvent this lack of reproducibility, molecular biology tools were used to produce a recombinant 27-kDa-molecular-mass antigen from this fungus; a sizable quantity of this antigen was obtained through fermentation of Escherichia coli DH5alpha, which is capable of expressing the fungal protein. The latter was purified by the Prep-Cell System (Bio-Rad); the recovery rate of the pure protein was approximately 6%. A battery of 160 human serum samples, consisting of 64 specimens taken at the time of diagnosis from patients with PCM representing the various clinical forms plus 15 serum specimens each from patients with histoplasmosis and aspergillosis, 10 each from patients with cryptococcosis and tuberculosis, 6 from patients with coccidioidomycosis, and 40 from healthy subjects, were all tested by an indirect enzyme-linked immunosorbent assay with the purified 27-kDa recombinant protein. The latter was used at a concentration of 1.0 microgram/well; there were three serum dilutions (1:1,000, 1:2,000, and 1:4,000). The experiment was repeated at least twice. The average sensitivity for both experiments was 73.4%; in comparison with the healthy subjects, the specificity for PCM patients was 87.5% while for patients with other mycoses, it was 58.7%. Important cross-reactions with sera from patients with aspergillosis and histoplasmosis were detected. The positive predictive value of the test was 90.4%. These results indicate that it is possible to employ recombinant antigenic proteins for the immunologic diagnosis of PCM and, by so doing, achieve high coverage rates. Furthermore, antigen reproducibility can now be ensured, thus facilitating inter- and intralaboratory standardization.
Human Taenia solium cysticercosis is a major cause of epilepsy in developing countries, and porcine infection causes widespread economic losses because of infested pork. Recently, the use of oxfendazole (OFZ) for porcine cysticercosis provided, for the first time, an effective, single-dose treatment. We performed a controlled study to determine the time required between treatment with a single dose of OFZ and the death of cysticerci to define its applicability as preslaughter treatment or as a field control measure. Twenty naturally infected pigs were included in this study. Sixteen received a single dose (30 mg/kg) of OFZ, and were killed in groups of four at one, two, four, and 12 weeks after treatment. Four untreated controls were killed at week 12. No adverse reactions to OFZ were noted. A clear decrease in viability and number of cysts was evident after the first week after therapy, but even at week 4 some viable cysticerci were found in all samples. Twelve weeks after treatment, all meat appeared clear and only minuscule scars remained, except in one animal that had viable brain cysts. This study confirms the efficacy of a single dose of 30 mg/kg of OFZ for porcine cysticercosis but demonstrates that preslaughter treatment of pigs with OFZ will not be useful in controlling cysticercosis. The inclusion of porcine treatment with OFZ in mass cysticercosis control programs is, however, highly promising because it is a simple, effective, inexpensive, and potentially sustainable method for decreasing the porcine reservoir of cysticercosis in disease-endemic countries.