RESUMEN
A commercial pMOS transistor (MOSFET), 3N163 from Vishay (USA), has been characterized as a low-energy proton beam dosimeter. The top of the samples' housing has been removed to guarantee that protons reached the sensitive area, that is, the silicon die. Irradiations took place at the National Accelerator Centre (Seville, Spain). During irradiations, the transistors were biased to improve the sensitivity, and the silicon temperature was monitored activating the parasitic diode of the MOSFET. Bias voltages of 0, 1, 5, and 10 V were applied to four sets of three transistors, obtaining an averaged sensitivity that was linearly dependent on this voltage. In addition, the short-fading effect was studied, and the uncertainty of this effect was obtained. The bias voltage that provided an acceptable sensitivity, (11.4 ± 0.9) mV/Gy, minimizing the uncertainty due to the fading effect (-0.09 ± 0.11) Gy was 1 V for a total absorbed dose of 40 Gy. Therefore, this off-the-shelf electronic device presents promising characteristics as a dosimeter sensor for proton beams.
RESUMEN
Submicroscopic Plasmodium infections in pregnancy are common in endemic areas, and it is important to understand the impact of these low-level infections. Asymptomatic, chronic infections are advantageous for parasite persistence, particularly in areas where the optimal eco-epidemiological conditions for parasite transmission fluctuate. In chronic infections, the persistence of the antigenic stimulus changes the expression of immune mediators and promotes constant immune regulation, including increases in regulatory T cell populations. These alterations of the immune system could compromise the response to routine vaccination. This study aimed to evaluate the effect of submicroscopic plasmodial infection with P. falciparum and P. vivax during pregnancy on the immune response to the tetanus toxoid vaccine in Colombian women. Expression of different cytokines and mediators of immune regulation and levels of anti-tetanus toxoid (TT) immunoglobulin (Ig)G were quantified in pregnant women with and without submicroscopic plasmodial infection. The anti-TT IgG levels were significantly lower in the infected group compared with the uninfected group. The expression of interferon (IFN)-γ, tumour necrosis factor (TNF) and forkhead box protein 3 (FoxP3) was significantly higher in the infected group, while the expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) and transforming growth factor (TGF)-ß was lower in the group of infected. In conclusion, submicroscopic Plasmodium infection altered the development of the immune response to the TT vaccine in Colombian pregnant women. The impact of Plasmodium infections on the immune regulatory pathways warrants further exploration.
Asunto(s)
Anticuerpos Antibacterianos/sangre , Malaria/inmunología , Plasmodium falciparum/fisiología , Plasmodium vivax/fisiología , Complicaciones Infecciosas del Embarazo/inmunología , Linfocitos T Reguladores/inmunología , Toxoide Tetánico/inmunología , Adolescente , Adulto , Enfermedad Crónica , Colombia , Citocinas/metabolismo , Femenino , Humanos , Inmunidad Heteróloga , Embarazo , Vacunación , Adulto JovenRESUMEN
In Colombia, Plasmodium resistance to antimalarials such as chloroquine and antifolates is a serious problem. As a result, the national Colombian health authorities are monitoring the efficacy of alternative drugs and schemes. The study of genetic polymorphisms related with drug resistance is required in the region. In vitro responses to chloroquine, quinine, mefloquine, amodiaquine, desethylamodiaquine, artesunate and dihydroartesunate were carried out by HRP ELISA. SNP analysis in Pfcrt and Pfmdr1 genes was performed by PCR-RFLP in 77 samples from the North West region of Colombia. In vitro resistance to chloroquine was high (74%), followed by mefloquine (30%) and desethylamodiaquine (30%). A positive correlation between the IC(50) of paired drugs was also detected. The allele Pfmdr1 N86 (wild) was present in 100% of the samples and 1246Y (mutant) in 92%. However, their presence did not correlate with in vitro drug resistance. Presence of the mutations K76T and N75E in Pfcrt was confirmed in all samples. Analysis of 4 codons (72, 74, 75 and 76) in pfcrt confirmed the presence of the haplotypes CMET in 91% and SMET in 9% of the samples.
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Antimaláricos/farmacología , Resistencia a Medicamentos/genética , Proteínas de Transporte de Membrana/genética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Plasmodium falciparum/efectos de los fármacos , Polimorfismo de Nucleótido Simple , Proteínas Protozoarias/genética , Amodiaquina/análogos & derivados , Amodiaquina/farmacología , Animales , Cloroquina/farmacología , Colombia/epidemiología , Humanos , Malaria Falciparum/epidemiología , Malaria Falciparum/parasitología , Mefloquina/farmacología , Pruebas de Sensibilidad Parasitaria , Plasmodium falciparum/genética , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
INTRODUCTION: Malignant tumors sometimes initiate as paraneoplastic syndromes even years before the most common symptoms appear. These first manifestations could be the key for the diagnosis of "occult" malignancy. METHODS: We report the case of a 66 year old man with a renal cell carcinoma. The first symptom was a paraneoplastic cerebellar degeneration appeared 6 years before the first urologic manifestations. CONCLUSIONS: A progressive cerebellar syndrome could be the first manifestation of a renal cell carcinoma, even years before the first urologic symptoms. We must suspect an occult neoplasia in such patients.
Asunto(s)
Carcinoma de Células Renales/diagnóstico , Neoplasias Renales/diagnóstico , Degeneración Cerebelosa Paraneoplásica/etiología , Anciano , Humanos , MasculinoRESUMEN
Pregnancy-associated malaria (PAM) poses a threat to both the mother and fetus, increasing the risk of severe maternal anemia, fetal growth restriction and low birth weight infants. Two vaccines are currently in development to protect women from Plasmodium falciparum in pregnancy. Both vaccine constructs target the ID1-DBL2X domain of VAR2CSA, a protein expressed on the surface of infected erythrocytes (IEs) that mediates parasite sequestration in the placenta. Although development of an effective vaccine may be hampered by ID1-DBL2X polymorphisms expressed by field isolates, a recent study showed that genetic variation of this domain in South American parasite populations is much lower than in other geographical locations. This suggests that a recombinant vaccine designed to be efficacious in Africa and Asia is likely to be efficacious in South America. However, these studies did not include Colombian parasite populations in their analyses, which are known to be genetically distinct from other South American parasite populations due to their independent introduction from Africa. Therefore, we sought to determine the genetic variation of the ID1-DBL2X domain in Colombian parasites to assess the potential efficacy of the vaccine against PAM in this region. Through sequence analysis and population genetics, we show that there is a low degree of genetic variation amongst Colombian parasite populations and that a vaccine containing conserved antigen variants for worldwide populations is likely to be protective against PAM in Colombia. Our analysis also points towards an African origin for Colombian parasite populations, and suggests that their introduction into Colombia was a recurrent process encompassing multiple introduction events.
Asunto(s)
Variación Genética , Vacunas contra la Malaria/inmunología , Malaria Falciparum/inmunología , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Plasmodium falciparum/inmunología , Adolescente , Adulto , Anticuerpos Antiprotozoarios/inmunología , Niño , Colombia , Femenino , Genética de Población , Genotipo , Humanos , Malaria Falciparum/prevención & control , Persona de Mediana Edad , Pruebas de Neutralización , Filogenia , Plasmodium falciparum/clasificación , Embarazo , Complicaciones Parasitarias del Embarazo/inmunología , Complicaciones Parasitarias del Embarazo/parasitología , Complicaciones Parasitarias del Embarazo/prevención & control , Proteínas Protozoarias/inmunología , Adulto JovenRESUMEN
The horseradish peroxidase (HRP), a glycoprotein rich in mannose and N-acetylglucosamine residues has been used as a ligand to detect receptors for N-glycosidic linked oligosaccharides of glycoproteins in the human spermatozoon. Specific binding of HRP occurred to the membrane and the binding sites were visualized with 3,3'-diaminobenzidine-H2O2 (DAB-H2O2) reagent, and by fluorescence when the FITC-peroxidase was used. This specific binding was suppressed by alpha-D-methyl-mannoside and human chorionic gonadotropin, decreased by follicle stimulating and luteinizing hormones and slightly diminished by N-acetylglucosamine. The distribution of the N-linked oligosaccharide specific receptors for glycoproteins in the different zones of the membrane of the spermatozoon was determined by counting the spermatozoa labeled in those zones. The pattern of the distribution is similar to that found for N-linked oligosaccharides containing glycoproteins of the same membrane. The similarity of these distributions together with the general model for cell-to-cell recognition suggest that the sperm-egg interaction mechanism could consist of dual interactions by double binding receptors.
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Glicoproteínas/metabolismo , Oligosacáridos/metabolismo , Complejo GPIb-IX de Glicoproteína Plaquetaria , Glicoproteínas de Membrana Plaquetaria , Receptores Inmunológicos/metabolismo , Espermatozoides/metabolismo , Membrana Celular/metabolismo , Histocitoquímica , Peroxidasa de Rábano Silvestre/metabolismo , Humanos , MasculinoRESUMEN
BACKGROUND: The aim of this study was to assess the effect of influenza vaccination on plasma HIV viral load and CD4 T-lymphocytes in patients with advanced HIV disease. PATIENTS AND METHOD: Observational study carried out in HIV-infected patients with a CD4 cell count < 200 X 10(6)on highly active antiretroviral therapy(HAART). Influenza vaccine was voluntarily offered and plasma viral load and CD4 cell counts were measured at baseline, 4 weeks and 12 weeks in vaccinated and control subjects. RESULTS: Sixteen patients were analysed, 10 of them being immunized with the influenza vaccine. A significant decline in CD4 cell counts at 4 and 12 weeks and an increasing trend of viral load were seen in all immunized patients who had a high viral load at the time of vaccination (n = 6), but not in those with an undetectable viral load. The mean decrease of CD4 T-lymphocytes in these 6 patients was 49.8%. Three patients showed a huge drop of the CD4 cell count (over 60% of baseline). CONCLUSIONS: Influenza vaccination of severely immunocompromised HIV-infected patients who are failing to HAART might be associated with an immunological impairment.
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Linfocitos T CD4-Positivos , Infecciones por VIH/sangre , Vacunas contra la Influenza , Carga Viral , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Huésped Inmunocomprometido , Masculino , Persona de Mediana Edad , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Primary lymphoma of the central nervous system (PLCNS) makes up 1% of all intracranial tumours and 1% of all lymphomas [1]. It has been described in different types of immunodeficiencies, but in recent years has been increasingly found in immunocompetent persons. The LPSNC are usually B cell tumours, so the T phenotype is yet another rare aspect. CLINICAL CASE: A 62-year-old man, smoker, BCO, presented with a clinical picture (for the previous month and a half) of holocranial headache, positive Valsalva manoeuvre, unsteadiness, tendence to retropulsion and difficulty in starting to walk. On physical examination there was deficient orientation in time and space, slight dysarthria, regressive reflexes and ataxia on walking. Cerebral CT scan and MR scans showed periventricular, thalamic and mesencephalic lesions with behaviour suggestive of a lymphoma. Neoplasia was confirmed on biopsy. Three months later, whilst on corticotherapy and holocranial radiotherapy, the patient died from intercurrent infection. CONCLUSIONS: To date, including the present case, 51 cases of T lymphoma have been described in immunocompetent patients. Our case showed aspects described in the literature. These were: more often made [2], more often infratentorial [2-4] and of poor prognosis with regard to the degree of histological malignancy [5].
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Encéfalo/patología , Linfoma de Células T/patología , Resultado Fatal , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: To design, implement and assess a clinical pathway for lower-extremity deep venous thrombosis, and to compare the length of hospital stay in two different periods. DESIGN: Development of the care pathway by a multidisciplinary team, followed by a controlled intervention study to compare two non-concomitant cohorts of patients corresponding to the years 2002 (before the implementation of the critical pathway) and 2004 (year of the implementation). SETTING: Academic tertiary care hospital. PARTICIPANTS: 90 patients, 42 corresponding to the year 2004 and 48 to 2002, admitted to hospital with a diagnosis of lower-extremity deep venous thrombosis (DVT). MAIN OUTCOME MEASURES: Length of hospital stay, hospitalisation costs and care indicators. RESULTS: The mean length of hospital stay was 6.78 days in 2002 and 4.72 days in 2004. This means a reduction of 2.06 days (p<0.012). The reduction in the length of hospital stay in 2004 situates the hospital 1.98 days below the mean stay of our community (6.7 days) for the same diagnosis and year. The impact of the clinical pathway was assessed using the following indicators: implementation indicator 92.2%, compliance indicator 65%, adverse events indicator 2.5% and satisfaction indicator 67%. In comparison with costs incurred in year 2002, implementation of the clinical pathway resulted in a saving of euro427.33 per patient and a total saving of euro17,093.20. CONCLUSIONS: The implementation of a lower-extremity DVT clinical pathway in our institution has help to reduce hospitalisation costs, due to a decreased length of hospital stay.
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Vías Clínicas/economía , Costos de la Atención en Salud , Extremidad Inferior , Trombosis de la Vena/economía , Trombosis de la Vena/terapia , Centros Médicos Académicos/organización & administración , Anciano , Anciano de 80 o más Años , Medicina Basada en la Evidencia , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Trombosis de la Vena/prevención & controlRESUMEN
The population structure of Plasmodium falciparum has been widely studied in diverse epidemiological contexts, but emphasis has been made in regions with high and stable transmission. In order to establish the genetic structure of P. falciparum in areas of Colombia with different degree of endemicity, we studied 100 samples from malaria patients of two different municipalities. The frequency of multiclonal infection in these areas and the correlation with the endemicity were carried out by comparison of the amplified products from polymorphic segments of MSP-1, MSP-2, and GLURP genes. We found low size polymorphism of the studied genes: 1 MSP-1 allele, 3 MSP-2 alleles, and 4 GLURP alleles. We conclude that the P. falciparum population in the regions studied is genetically homogeneous.
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Variación Genética , Malaria Falciparum/parasitología , Plasmodium falciparum/genética , Adolescente , Adulto , Alelos , Animales , Antígenos de Protozoos/genética , Niño , Colombia/epidemiología , Femenino , Humanos , Malaria Falciparum/epidemiología , Masculino , Proteína 1 de Superficie de Merozoito/genética , Polimorfismo Genético , Proteínas Protozoarias/genética , Población RuralRESUMEN
Protective immune mechanisms to the asexual erythrocytic stages of the malaria parasite Plasmodium chabaudi AS strain include antibody-independent mechanisms. Nitric oxide (NO) is produced during the infection and indirect evidence suggests that it can contribute to the antiparasitic mechanisms. We examined the effect of an NO producer, S-nitroso-acetyl-penicillamine (SNAP), on the growth and survival in vitro of P. chabaudi AS, P. berghei and P. falciparum. Growth of the parasites was monitored by the uptake of tritiated hypoxanthine and, in the case of P. falciparum, by morphological examination in stained blood smears. DL-penicillamine and sodium nitrite, as controls, had no inhibitory activity at the concentrations used. The results showed that at SNAP concentrations of approximately 182 microM and above NO was cytotoxic to P. falciparum but, at lower concentrations, there was a cytostatic effect and some parasites resumed growth and division after NO production had ceased. Rings were less susceptible to NO effects than later stages in the asexual cycle. The antimalarial activity of NO from SNAP also extended to the rodent parasites but, under the experimental conditions used, they were less sensitive than the human species. In the cultures of P. chabaudi, increasing the numbers of noninfected erythrocytes present did not diminish the antimalarial activity of SNAP, suggesting that here at least haemoglobin was not scavenging NO significantly.
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Antimaláricos/farmacología , Óxido Nítrico/farmacología , Plasmodium berghei/efectos de los fármacos , Plasmodium chabaudi/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Eritrocitos/parasitología , Femenino , Humanos , Hipoxantina/metabolismo , Malaria/sangre , Malaria/parasitología , Masculino , Ratones , Parasitemia , Penicilamina/análogos & derivados , Penicilamina/farmacología , Plasmodium berghei/crecimiento & desarrollo , Plasmodium berghei/metabolismo , Plasmodium chabaudi/crecimiento & desarrollo , Plasmodium chabaudi/metabolismo , Plasmodium falciparum/crecimiento & desarrollo , Plasmodium falciparum/metabolismo , TritioRESUMEN
Urethral diverticula with calculi are rare. This 5x6 cm calculus presented in a patient with recurrent urinary tract infections. Local excision was effective.
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Divertículo/complicaciones , Enfermedades Uretrales/complicaciones , Cálculos Urinarios/complicaciones , Anciano , Anciano de 80 o más Años , Cistoscopía , Divertículo/diagnóstico , Divertículo/cirugía , Femenino , Humanos , Enfermedades Uretrales/diagnóstico , Enfermedades Uretrales/cirugía , Cálculos Urinarios/diagnóstico , Cálculos Urinarios/cirugía , UrografíaRESUMEN
Introducción: Los procesos tumorales pueden de manera ocasional mostrar su primera manifestación con una sintomatología neurológica, no originada por metástasis, sino del denominado tipo paraneoplásico, que puede aparecer incluso años antes de los síntomas habituales del tumor. Este tipo de manifestaciones iniciales pueden ser la clave del descubrimiento de una neoplasia oculta. Métodos: Presentamos el caso de un varón de 66 años afecto de un carcinoma renal, cuya manifestación inicial consistió únicamente en un cuadro neurológico progresivo de tipo cerebeloso paraneoplásico, aparecido 6 años antes de la primera sintomatología urológica. Conclusiones: La aparición de una sintomatología neurológica cerebelosa progresiva puede ser la única y primera manifestación de un carcinoma renal, incluso años antes de las primeras manifestaciones urológicas. Debe sospecharse la existencia de una neoplasia oculta en los pacientes con esta sintomatología (AU)
Introduction: Malignant tumors sometimes initiate as paraneoplastic syndromes even years before the most common symptoms appear. These first manifestations could be the key for the diagnosis of 'occult' malignancy. Methods: We report the case of a 66 year old man with a renal cell carcinoma. The first symptom was a paraneoplastic cerebellar degeneration appeared 6 years before the first urologic manifestations. Conclusions: A progressive cerebellar syndrome could be the first manifestation of a renal cell carcinoma, even years before the first urologic symptoms. We must suspect an occult neoplasia in such patients (AU)
Asunto(s)
Humanos , Masculino , Anciano , Degeneración Cerebelosa Paraneoplásica/etiología , Neoplasias Renales/complicaciones , Neoplasias Renales/diagnóstico , Tomografía Computarizada por Rayos X , Imagen por Resonancia MagnéticaAsunto(s)
Endocarditis Bacteriana/microbiología , Infecciones por Erysipelothrix/microbiología , Erysipelothrix/aislamiento & purificación , Explotaciones Pesqueras , Enfermedades Profesionales/microbiología , Adulto , Insuficiencia de la Válvula Aórtica/etiología , Bacteriemia/microbiología , Endocarditis Bacteriana/complicaciones , Endocarditis Bacteriana/diagnóstico , Infecciones por Erysipelothrix/complicaciones , Infecciones por Erysipelothrix/diagnóstico , Traumatismos de los Dedos/microbiología , Humanos , Masculino , Enfermedades Profesionales/diagnóstico , Microbiología del SueloAsunto(s)
Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de la Proteasa del VIH/efectos adversos , Pancreatitis/inducido químicamente , Ritonavir/efectos adversos , Enfermedad Aguda , Adulto , Fármacos Anti-VIH/uso terapéutico , Quimioterapia Combinada , Inhibidores de la Proteasa del VIH/uso terapéutico , Humanos , Hipertrigliceridemia/inducido químicamente , Masculino , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Ritonavir/uso terapéutico , Combinación Trimetoprim y Sulfametoxazol/uso terapéutico , Zidovudina/uso terapéuticoAsunto(s)
Brucella melitensis , Brucelosis/patología , Endocarditis Bacteriana/patología , Adulto , Animales , Antibacterianos/uso terapéutico , Brucella melitensis/aislamiento & purificación , Brucelosis/tratamiento farmacológico , Brucelosis/microbiología , Doxiciclina/uso terapéutico , Endocarditis Bacteriana/tratamiento farmacológico , Endocarditis Bacteriana/microbiología , Humanos , Masculino , Rifampin/uso terapéutico , Estreptomicina/uso terapéuticoRESUMEN
El asma bronquial es la patología crónica con mayor prevalencia en la infancia, con un progresivo aumento en su morbi-mortalidad. Los factores emocionales juegan un papel importante en el desencadenamiento, evolución, mantenimiento y recuperación de las crisis asmáticas. En este trabajo hacemos un recorrido por la personalidad del niño asmático, las características e influencia de la familia y su entorno social, las principales alteraciones psicológicas asociadas con el asma y los tratamientos más utilizados según las diferentes teorías psicológicas
Bronchial asthma is the chronic pathology with highest prevalence in childhood, showing a progressive increase in morbidity and mortality. Emotional factors play an important role in the onset, development, duration and recovery of the asthmatic crisis. In this paper we summarize the asthmatic child's personality profile, the characteristics and influence of the family and social environment in the development of the disease, the main psychological disorders associated with asthma and the most common treatment strategies according to different psychological theories
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Humanos , Niño , Asma/etiología , Asma/psicología , Familia/psicología , Depresión/complicaciones , Ansiedad/complicaciones , Trastornos Mentales/complicaciones , Teoría Psicológica , Asma/terapiaRESUMEN
Objetivo. Identificar a mujeres con neoplasia cervical entre pacientes diagnosticadas de ASCUS, mediante colposcopia; se compara el estudio de PCR para el VPH con la repetición de una citología cervicovaginal. El fin es determinar si la PCR para VPH es útil en la evaluación de pacientes diagnosticadas de ASCUS y si puede ser un método alternativo a la repetición de la citología cervical. Material y métodos. Se estudia a 180 mujeres diagnosticadas de ASCUS, y se realiza una colposcopia, una nueva citología, PCR para VPH y estudio histológico de las biopsias cervicales. Las pacientes con resultados negativos se controlaron de nuevo a los 6 meses. Resultados. La PCR fue positiva en el 34% de las pacientes y negativa en el 66%. No se encontró lesión cervical en el 69%, había condiloma o CIN I en el 21% y CIN II o CIN III en el 10%. Cuando aplicamos el teorema de Bayes, para la PCR, la sensibilidad fue del 60%, la especificidad del 80%, el VPP del 61% y el VPN del 79%; para la citología, la sensibilidad fue del 64%, la especificidad del 88%, el VPP del 71% y el VPN del 84%, incluidas como positivas las citologías repetidamente diagnosticadas de ASCUS. Conclusiones. En nuestro estudio, tanto la citología repetida posterior como la investigación de PCR para VPH tienen valores de sensibilidad, especificidad, VPP y VPN parecidos, y sus intervalos de confianza son similares. Destaca el valor predictivo negativo del 94% para la PCR, y es el método más apropiado para identificar a las mujeres que no enfermarán (AU)
Objective. To identify women with cervical neoplasia amongst those patients diagnosed as having ASCUS after colposcopy and comparing the PCR study for human papilloma virus (HPV) with a repeat cervico- vaginal histology. Also, to determine if PCR for HPV is useful in patients diagnosed as ASCUS, and if it may be an alternative to repeat cervical cytology. Material and methods. A study was made of 180 women, after colposcopy, repeat cytology, PCR for HPV, and a histological study of the cervical biopsies. Results. PCR was positive in 34% of the patients and negative in the other 66%. No cervical lesion was found in 69%, there was condilloma or CIN I in 21% and CIN II or CIN III in 10%. Applying Bayes theorem, sensibility for PCR was 60%, specificity was 80%, VPP 61% and VPN 79%; for cytology, the sensibility was 64%, specificity 88%, VPP 71% and VPN 84%, including as positive those smear test repeatedly diagnosed as ASCUS. Conclusions. In our study, repeat cytology and PCR testing for HPV had similar sensibility, specificity, VPP and VPN values, the confidence intervals were also similar. We highlight the 94% negative predictive value for PCR, this being the most appropriate method to identify those women who are not going to develop disease (AU)