[Primary prevention of colorectal cancer].
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Biomedical subjects
Publications and source records attributed to V Moreno.
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BACKGROUND: the efficacy of zidovudine (ZDV) is lost in many treated individuals after a few weeks or months of monotherapy. The development of drug resistance seems to explain this adverse event. However, some individuals seem to persistently benefit clinically and immunologically from ongoing ZDV monotherapy. The degree and causes of this phenomenon remain unclear. PATIENTS AND METHODS: we studied 280 HIV-infected patients who have been receiving ZDV monotherapy for more than 18 months (mean 28 +/- 7 months), and whom has a CD4+ count between 200 and 500 x 10(6)/l at baseline. We classified them into two groups: Non-progressors with ZDV (NP-ZDV), subjects with an increase or a reduction < 15% in the CD4+ count; and Progressors with ZDV (P-ZDV), subjects showing a decline in the CD4 count > 15%. Epidemiological, immunological and virological features of each group were compared. RESULTS: the prevalence of NP-ZDV in this population was 15.7% (44/280). Age, gender, and risk behaviour were not significantly different in NP-ZDV and P-ZDV. Although the CD4/CD8 ratio, as well as the CD45R0/CD45RA ratio into the CD4+ subpopulation, were higher in NP-ZDV than in P-ZDV, the values did not achieve statistical significance. Virological studies were performed on 36 (81.8%) NP-ZDV and 55 (23.3%) P-ZDV. Mean HIV-RNA titer was higher in P-ZDV than in NP-ZDV (8.4 x 10(4) vs. 1.5 x 10(3) copies/ml; p < 0.01). Virus isolation from circulating mononuclear cells was made more frequently in P-ZDV than in NP-ZDV (90.9% vs. 81.5%), although it did not achieve statistical significance. The syncitium-inducing (SI) phenotype was detected in more than a quarter (27.3%) of P-ZDV but was absent in NP-ZDV (p < 0.01). The prevalence of RT mutations at codon 215 was much lower in NP-ZDV than in P-ZDV, and it showed a strong statistical significance (13.9% vs. 74.5%; p < 0.01). CONCLUSIONS: prolonged (> 2 years) lack of immunological and clinical progression can be observed in 15% of HIV-infected persons with mild immunosuppression, undertaking ZDV monotherapy. This effect seems to be associated with a characteristic virological profile, in which a low viral load, the absence of SI phenotype, and a lack of development of ZDV-resistance are the most relevant features.
BACKGROUND: The rate of progression to AIDS in HIV-1 infected subjects is variable, and circumstances associated with more rapid or slow development of severe immunodeficiency might be grouped in three categories; environmental cofactors, host features, and particular virulence of the virus itself. Currently, it is not yet clear the the relative impact of each one. PATIENTS AND METHODS: A cross-sectional study was done in a cohort of 1,783 IV-1 infected persons from three centers located in Madrid, mainly devoted to attend persons at risks for HIV infection. Long-term nonprogressors (LTNP) were defined as those with more than 8 years of confirmed HIV seropositivity, and CD4+ T-cell count above 500 x 10(6)/I in the absence of antiretroviral therapy or symptoms suggesting immunodeficiency. Rapid progressors (RP) were those with less than 5 years from seroconversion and repeatedly current CD4+ T-cell count below 200 x 10(6)/I. An analysis of different epidemiological, immunological and virological features was performed comparing LTNP and RP. RESULTS: Among 1,783 HIV (+) subjects studied, 100 (5.6%) fulfilled criteria for LTNP and 12 (0.7%) for RP. Among LTNP, stabilized CD4 slope was seen in 16 (33%) out of 48 after more than 8 years of infection. Variables statistically associated with LTNP were: past history of intravenous drug addiction (80% of them), male gender (79% of them), high alcohol intake (48% of them), HIV-1 non-syncitium inducing viral phenotype, and very low or undetectable HIV-1 plasma viremia. In contrast, variables associated with RP were: infection by sexual contact (75% of cases), female gender (50% of them), syncitium-inducing viral plenotype, and high titers of plasma viremia. The CD4/CD8 ratio below 1 was seen in all RP and in 88% of LTNP. However, a preferent depletion of CD4+ cell occurred in the first group, instead of an enhancement of the CD8 T-cell count in LTNP. The prevalence of serological markers for hepatotropic viruses and other potential infectious cofactors was not higher in RP. CONCLUSIONS: Multiple factors seems to account for the different rate of disease progression observed in HIV-1 infected persons. The dynamic equilibrium between the immune system and the virulence of the virus seem to be influenced--but not determined--by environmental infectious or non infectious cofactors.
BACKGROUND: To evaluate the risk of developing breast cancer among Catalan women and to estimate the number of new cases of this tumor that appear annually in Catalonia (north-east of Spain). MATERIAL AND METHODS: The incidence rates of breast cancer were used in the period 1985-1989 proceeding from the population-based cancer registries of Tarragona and Girona. The age-specific rates (ASR) in Catalonia were estimated by an ASR average of Girona and Tarragona, that were adjusted by the standardized mortality ratio (SMR) of these health regions in relation to Catalonia. The cumulative rate and the risk of developing breast cancer were calculated, considering the probability of death by other causes. The temporal trend of breast cancer incidence was analysed by the Poisson's regression model. RESULTS: The cumulative risk (0-74 years) for breast cancer among Catalan women was 5.17% (1 out of 19 women). The highest risk of developing breast cancer is in the group of age between 60 and 79 years old. Tarragona and Girona had both a moderate increase that was not statistically significant. About 2,550 new cases of breast cancer have been estimated in 1994 and 2,600 in 1996. CONCLUSION: The risk of developing breast cancer in Catalonia after adjusting for the probability of dying by other causes, is lower than in other countries of Northern Europe and the United States.
BACKGROUND: To analyze the perception of causes and prevention of cancer among women, from Girona, Spain, as well as to assess the knowledge of initial symptoms and participation in cancer screening activities. SUBJECTS AND METHODS: Crossectional survey with the following items: cancer risk factors, initial symptoms, perceived susceptibility, knowledge and practice of screening, beliefs regarding prevention and treatment of cancer, intention to attend screening tests and socio-demographic variables. A stratified random sample of 408 women aged 40 to 70 from two counties in Girona, Spain was selected. RESULTS: More than 80% of women identified tobacco, radioactivity and other environmental factors as causes of cancer, being the alcohol identified by 70% of women. It was clearly observed that a high level of these women (97.5%) considered a lump in the breast as an initial symptom of cancer, whereas only a 6.6% thought it was always due to cancer. With regard to cancer screening, 21.9% of women have ever practiced a mammography, 28.5% a cervical citology with Papanicolaou staining and 53.2% self-breast examinations. All these screening activities were inversely associated to age (p < 0.05) and directly to educational level (p < 0.05). CONCLUSION: A high knowledge regarding the causes of cancer with the exception of diet was observed in women from Girona, Spain. Knowledge and participation in screening activities is still low in practice of population cancer screening programmes.
The authors propose a method to perform a combined analysis of matched and unmatched case-control studies that is based on an adaptation of logistic regression and can be performed using standard software. This methodology can be used to do pooled analyses of studies with different designs. Likelihood ratio tests can be performed to assess association, heterogeneity, or trend. The standard errors of the coefficients allow the derivation of a Wald test and the calculation of confidence intervals. Another application is to compare relative risk estimators for the same risk factors studied in different phases of a disease in an effort to explore factors that may be more important in one phase than in another. Interaction terms of risk factors with variables that code the different pooled studies can be used for this purpose. The advantage of using this method is that a formal statistical comparison can be performed in which the regression coefficients of the interaction terms estimate the relative differences in risk (odds ratio ratios) between the studies. This estimation can be adjusted for other confounder factors. Two examples of application using data from case-control studies on cervical cancer and colorectal cancer are presented to illustrate the use of this epidemiologic method.
The use of pure follicle stimulating hormone (pFSH) and highly purified FSH (FSH-HP) versus the combinations pFSH/human menopausal gonadotrophin (HMG) and FSH HP/HMG, respectively, was compared for stimulating follicular development after gonadotrophin-releasing hormone agonist (GnRHa) suppression in women undergoing in vitro fertilization (IVF)-embryo transfer. Two consecutive prospective, randomized studies were carried out at the Assisted Reproduction Unit of the Hospital Clínic i Provincial in Barcelona, a tertiary care setting. Two groups of 188 (study 1) and 252 (study 2) consecutive infertile patients respectively, scheduled for IVF-embryo transfer were included. Pretreatment with leuprolide acetate (long protocol) was followed by gonadotrophin treatment in all patients. In study 1, 92 patients received i.m. pFSH alone (group pFSH) and 96 were treated with the combination of i.m. pFSH and i.m. HMG (group HMG-1). In study 2, 123 patients received s.c. FSH-HP alone (group FSH-HP) and 129 patients were given the combination of s.c. FSH-HP and i.m. HMG (group HMG-2). Main outcome measures included follicular development, oocyte retrieval, fertilized oocytes, duration and dose of gonadotrophin therapy, and clinical pregnancy. There were no significant differences between pFSH and pFSH/HMG nor between FSH-HP and FSH-HP/HMG cycles with regard to the number of ampoules of medication used, day of human chorionic gonadotrophin (HCG) administration, mean peak serum oestradiol concentrations, number of follicles punctured, and number of oocytes aspirated, embryos transferred, or pregnancies. We conclude that urinary FSH (either purified of highly purified) alone is as effective as the conventional combination of urinary FSH/HMG for ovarian stimulation under pituitary suppression in IVF cycles. Therefore, they can be used interchangeably in IVF programmes.
The effect of Colcemid on the frequency and type of chromosomal abnormalities in human sperm was investigated. Using the human sperm and zona-free hamster egg fusion technique, penetrated eggs were cultured in the presence or absence of Colcemid. We used two different times of Colcemid treatment: standard Colcemid treatment (Colcemid-5 h) or long Colcemid treatment (Colcemid-17 h). Each Colcemid series had its own control series without Colcemid, thus ensuring that Colcemid was the only significant variable. A total of 771 sperm karyotypes from one normal donor was analyzed: 286 in the Colcemid-5 h series, 262 in the Colcemid-17 h series, and 223 in the two control series. In both Colcemid series there was a significant increase in the frequencies of hypohaploidy vs. hyperhaploidy (9.4% and 7.3% vs. 2.4% and 1.1%, for the Colcemid-5 h and Colcemid-17 h series, respectively), in contrast to those obtained in the control series, in which the frequencies of hypohaploidy and hyperhaploidy were close to the 1:1 relationship (4.9% vs. 4.0%) expected from nondisjunction. There was a significant increase in the frequency of structural abnormalities in both Colcemid series (16.1% and 14.5% for the Colcemid-5 h and Colcemid-17 h series, respectively) compared to the control series (6.3%). These results suggest that Colcemid significantly increases the frequency of hypohaploidy and unstable structural aberrations in human sperm.
OBJECTIVE: it is analyzed a group of patients with HIV related malignancy treated with myelosuppressive therapy with granulocyte colony stimulating factor (G-CSF) to study the efficacy of hematopoietic growth factors in these subjects. PATIENTS AND METHODS: it was studied the clinical and hematological evolution of 20 patients with HIV related malignancy treated with standard dose of chemotherapy and 5 micrograms/Kg/day of G-CSF starting 24 hours after the completion of chemotherapy administration. It was done an epidemiological study and was determined haemoglobin level, and the number of leukocytes, monocytes, neutrophils, lymphocytes, CD4+ lymphocytes and platelets before and after the chemotherapy administration. RESULTS: all of the patients were men with mean age of 37 +/- 2 years. The mean of lymphocyte CD4+ count was 17 x 10(6)/l and the tumor was the first aids manifestation in 50% of the subjects. The mean days of hospitalization was 14 +/- 3 days. As the result of the G-CSF administration, the leucocyte and the neutrophil count was statistically elevated (p < 0.01) and the platelets, the lymphocytes and the monocytes were not statistically elevated. Only one patient had a severe adverse reaction. Seventeen patients (85%) are dead, but only in 3 the cause was an infectious disease. CONCLUSION: the use of G-CSF prophylactically can elevate the neutrophil count and avoid the apparition of febrile neutropenia in patients with HIV related malignancies.
An HIV-infected woman with a CD4+ T-cell count below 100 x 10(6)/l survived for longer than 4 years of being diagnosed of AIDS, with acceptable health status (Karnofsky > 80%). Administration of foscarnet during two years, recommended as suppressive therapy for a previous cytomegalovirus retinitis, might have caused a sustained reduction in plasma HIV-RNA, contributing to her long-term survival.
Lymphomatous meningitis and lymphoma confined to the central nervous system are the most serious neurological diseases in patients with human immunodeficiency virus infection. The diagnosis is difficult and it is usually done with advanced systemic disease or when the chemotherapy is finished. During a ten month period, three patients with lymphomatous meningitis and HIV infection were diagnosed in an Infectious Diseases Unit. In one patient, was the initial clinical manifestation of Burkitt's lymphoma and in another, the diagnosis was concomitant with the neoplasm. In the last one, there was a meningeal recidiva afterwards he had received chemotherapy and, theoretically, cured his systemic lymphoma. Clinical, cytologic, immunologic and evolutive study of these three patients is done. It is discussed the meningeal prophylaxis usefulness with intrathecal chemotherapy.
BACKGROUND: Tuberculosis (TB) with liver and/or spleen abscess (HSA) formation in HIV-positive patients is uncommon. PATIENTS AND METHODS: One hundred and thirty-seven HIV positive patients with TB were studied from January 93 to June 95. Patients with tuberculous HSA were enrolled in the study. Diagnosis was obtained by recovery of Mycobacterium tuberculosis in clinical specimens and the presence of hypoechogenic lesions in liver and/or spleen. RESULTS: M. tuberculosis isolates were resistant to some of the usual drugs in 51 patients. Twenty of these patients had HSA (39%) and in 18 patients the antibiotic sensitivity testing showed resistance to isoniazid, rifampin, ethambutol, and streptomycin. The remaining 86 patients had episodes of TB with drug-susceptible microorganism and only three patients had HSA (3%) (p < 0.001). The 23 patients with tuberculous HSA had a mean CD4+ lymphocyte count of 33 x 10(6) cells/L (2-111) and 7 had a previous episode of TB. The abdominal echography showed hepatosplenomegaly in all cases. Abscesses were located at the liver in 12 patients (52%), spleen in 18 (78%) and both organs in 7 (30%). In 16 cases a corticosteroid therapy was indicated. In the 3 patients with susceptible TB and HSA the clinical course was good. The 20 patients with resistant TB died. CONCLUSION: Abdominal TB in HIV-positive patients and HSA formation appears to be more common in severely immunosuppressed patients, with resistant TB and its mortality rate is high. The response to therapy with antituberculous drugs is slow and sometimes the administration of corticosteroids is necessary for the resolution of symptoms.
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OBJECTIVE: To study the present and preferred sources of information about cancer. DESIGN: Cross-sectional study. PLACE: Counties of Gironés and Pla de l'Estany from the province of Girona. PARTICIPANTS: Stratified random sample of 408 women aged 40 to 70 years. RESULTS: Main present source of information about cancer were friends and relatives (34.9%), followed by radio and Tv (34.0%) and newspapers (19.9%). Health care professionals only were considered main source of information by 11.3% of the sample. Women with incomplete primary school and women from older age groups answered more frequently Radio and Tv as their main source of information. However, the preferred source of information about cancer were health care professionals (73.3%). CONCLUSION: Health care professionals are the preferred source of information about cancer but only a small percentage of population receive information from them. These results indicate the need to redefine educational strategies regarding cancer in primary health care.
BACKGROUND: Epidemiologic studies have shown that the association of genital human papillomavirus (HPV) with cervical cancer is strong, independent of other risk factors, and consistent in several countries. There are more than 20 different cancer-associated HPV types, but little is known about their geographic variation. PURPOSE: Our aim was to determine whether the association between HPV infection and cervical cancer is consistent worldwide and to investigate geographic variation in the distribution of HPV types. METHODS: More than 1000 specimens from sequential patients with invasive cervical cancer were collected and stored frozen at 32 hospitals in 22 countries. Slides from all patients were submitted for central histologic review to confirm the diagnosis and to assess histologic characteristics. We used polymerase chain reaction-based assays capable of detecting more than 25 different HPV types. A generalized linear Poisson model was fitted to the data on viral type and geographic region to assess geographic heterogeneity. RESULTS: HPV DNA was detected in 93% of the tumors, with no significant variation in HPV positivity among countries. HPV 16 was present in 50% of the specimens, HPV 18 in 14%, HPV 45 in 8%, and HPV 31 in 5%. HPV 16 was the predominant type in all countries except Indonesia, where HPV 18 was more common. There was significant geographic variation in the prevalence of some less common virus types. A clustering of HPV 45 was apparent in western Africa, while HPV 39 and HPV 59 were almost entirely confined to Central and South America. In squamous cell tumors, HPV 16 predominated (51% of such specimens), but HPV 18 predominated in adenocarcinomas (56% of such tumors) and adenosquamous tumors (39% of such tumors). CONCLUSIONS: Our results confirm the role of genital HPVs, which are transmitted sexually, as the central etiologic factor in cervical cancer worldwide. They also suggest that most genital HPVs are associated with cancer, at least occasionally. IMPLICATION: The demonstration that more than 20 different genital HPV types are associated with cervical cancer has important implications for cervical cancer-prevention strategies that include the development of vaccines targeted to genital HPVs.
BACKGROUND: The natural course of the human immunodeficiency virus type 1 (HIV-1) infection is very variable. The factors which appear to determine the speed of immunodeficiency progression are multiple, although the virulence of the predominant viral strain seems to be one the main factors. The plasmatic viremia in individuals with rapid and slow HIV-1 progression was analyzed in an attempt to establish the degree of correlation between HIV-1 replication and the natural course of the disease. METHODS: Forty-two samples from 34 seropositive patients, 11 with rapid progression criteria (< 5 years from acute infection and CD4+ lymphocytes < 0.2 x 10(9)/l) and 23 with slow progression (> 7 years from demonstrated infection and > 0.5 x 10(9) CD4+ lymphocytes/l) were studied. The plasmatic viremia was quantified by a new method of plasma DNA genetic amplification, denominated the branched DNA (bDNA) technique. As a reference circulating p24 was determined and the presence of several proviral regions were studied in peripheral blood lymphocytes by polymerase chain reaction (PCR). RESULTS: The presence of RNA molecules was detected in plasma of 7 (58.3%) out of 12 samples of rapid progression (RP) patients by bDNA. To the contrary, this was negative in 30 samples from slow progression (SP) patients. Four of the 5 negative RP samples corresponded to patients who had taken antiretroviral drugs at the time of the study. The p24 antigenemia was positive in 5 (41.6%) from the RP patients and in none of the SP patients. The presence of gag, pol and env sequences was positive by PCR in all RP patients and in most of the SP patients. However, repeatedly negative results by PCR were observed in 5 SP samples for all or some of the genomic regions studied. CONCLUSIONS: Patients with rapid progression of HIV-1 have higher plasmatic viremia than subjects with slow disease progression.
Oxidative stress is involved in a multitude of pathological conditions. In the present study, we investigated the cellular targets and the mechanisms of low-level oxidative stress in a Chinese Hamster Ovary cell culture. Oxidative stress was induced either by continuous enzymatic production of superoxide or by bolus addition of hydrogen peroxide (H2O2). Low-level oxidative stress irreversibly impaired the reproductive capacity of the cells in the absence of damage to membrane integrity or energy metabolism. Cells were protected by catalase but not by superoxide dismutase, indicating that H2O2, not superoxide, was the causative agent of cell damage. Nitroxide spin labels decreased hydroxyl radical (.OH) formation and protected cells from the oxidative stress. The differing membrane permeabilities of these spin labels suggest that the damage is localized on the cell surface. Oxidative stress to DNA and RNA was not significant, as shown by levels of guanine hydroxylation products. A mechanism is proposed whereby low-level oxidative stress acts at the cell surface to cause impairment of cell reproduction.
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