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1.
Ann Oncol ; 25(6): 1152-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24692579

ABSTRACT

BACKGROUND: Breast cancer is a heterogeneous disease defined by both germline and somatic abnormalities. In preclinical models, tumors carrying homologous recombination defects are highly sensitive to trabectedin. This phase II trial evaluated the efficacy and safety of trabectedin in BRCA1/2 germline mutation carriers with pretreated metastatic breast cancer (MBC). PATIENTS AND METHODS: Trabectedin 1.3 mg/m(2) as a 3-h i.v. infusion was administered every 3 weeks until progression or intolerance. The primary efficacy end point was the objective response rate (ORR) as per RECIST. Secondary efficacy end points comprised time-to-event end points, and changes in tumor volume and expression of tumor marker CA15.3. Safety was evaluated using the NCI-CTCAE. RESULTS: Forty BRCA1/2 germline mutation carriers with MBC were included. Confirmed partial response (PR) occurred in 6 of 35 assessable patients [ORR = 17%; 95% confidence interval (CI) 7% to 34%] and lasted 1.4-6.8 months. Median PFS was 3.9 months (95% CI 1.6-5.5 months). Eight patients (21%) showed changes in tumor volume, and 14 (40%) a clinical benefit. Trabectedin-related adverse events were generally mild/moderate, the most common being fatigue, nausea, constipation and anorexia. Severe laboratory abnormalities (neutropenia, transaminase increases) were mostly transient and noncumulative, and were managed by dose adjustments. CONCLUSIONS: With the caveat of the limited patient number, trabectedin monotherapy showed activity and was well tolerated in heavily pretreated MBC patients selected for germline BRCA mutation. These results prompt further evaluation of trabectedin alone or combined with other specific drugs in this indication. CLINICALTRIALSGOV: NCT00580112.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Breast Neoplasms/drug therapy , Dioxoles/therapeutic use , Tetrahydroisoquinolines/therapeutic use , Adult , Breast Neoplasms/genetics , Breast Neoplasms/mortality , Disease-Free Survival , Female , Genes, BRCA1 , Genes, BRCA2 , Germ-Line Mutation , Humans , Kaplan-Meier Estimate , Middle Aged , Trabectedin
2.
Ann Oncol ; 23(3): 771-776, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21642514

ABSTRACT

BACKGROUND: To evaluate neoadjuvant trabectedin (1.5 mg/m(2) 24-h i.v. infusion every 3 weeks; three to six cycles) in patients with locally advanced myoxid liposarcoma (ML) previously untreated with chemotherapy or radiation. PATIENTS AND METHODS: Primary efficacy end point was pathological complete response (pCR) or tumoral regression rate. Objective response according to RECIST (v.1.0) was a secondary end point. RESULTS: Three of 23 assessable patients had pCR [13%; 95% confidence interval (CI), 3% to 34%]. Furthermore, very good and moderate histological responses were observed in another 2 and 10 patients, respectively. Histological decrement in the cellular and vascular tumor component and maturation of tumor cells to lipoblasts were observed in both myoxid and myoxid/round cell variants. Seven patients had partial response according to RECIST (objective response rate of 24%; 95% CI, 10% to 44%). No disease progression was reported. Neoadjuvant trabectedin was usually well tolerated, with a safety profile similar to that described in patients with soft tissue sarcoma or other tumor types. CONCLUSION: Trabectedin 1.5 mg/m(2) given as a 24-h i.v. infusion every 3 weeks is a therapeutic option in the neoadjuvant setting of ML.


Subject(s)
Antineoplastic Agents, Alkylating/therapeutic use , Dioxoles/therapeutic use , Liposarcoma, Myxoid/drug therapy , Neoadjuvant Therapy , Tetrahydroisoquinolines/therapeutic use , Adult , Aged , Female , Humans , Male , Middle Aged , Trabectedin , Young Adult
3.
Ann Oncol ; 23(5): 1234-1240, 2012 May.
Article in English | MEDLINE | ID: mdl-21930687

ABSTRACT

BACKGROUND: This multicenter phase II trial evaluated the efficacy and safety of trabectedin in metastatic castration-resistant prostate cancer (CRPC). PATIENTS AND METHODS: Two schedules were evaluated in three cohorts: weekly as 3-h i.v. infusion at 0.58 mg/m(2) for 3 out of 4 weeks (Cohort A, n = 33), and every 3 weeks (q3wk) as 24-h infusion at 1.5 mg/m(2) (Cohort B1, n = 5) and 1.2 mg/m(2) (Cohort B2, n = 20). The primary end point was prostate-specific antigen (PSA) response; secondary end points included safety, tolerability and time to progression (TTP). RESULTS: Trabectedin resulted in PSA declines ≥ 50% in 12.5% (Cohort A) and 10.5% (Cohort B2) of patients. Among men pretreated with taxane-based chemotherapy, PSA response was 13.6% (Cohort A) and 15.4% (Cohort B2). PSA responses lasted 4.1-8.6 months, and median TTP was 1.5 months (Cohort A) and 1.9 months (Cohort B2). The dose of 1.5 mg/m(2) (approved for soft tissue sarcoma) given as 24-h infusion q3wk was not tolerable in these patients. At 1.2 mg/m(2) q3wk and 0.58 mg/m(2) weekly, the most common adverse events were nausea, fatigue and transient neutropenia and transaminase increase. CONCLUSIONS: Two different trabectedin schedules showed modest activity in metastatic CRPC. Further studies may require identification of predictive factors of response in prostate cancer.


Subject(s)
Dioxoles/therapeutic use , Prostatic Neoplasms/drug therapy , Sarcoma/drug therapy , Tetrahydroisoquinolines/therapeutic use , Adult , Aged , Aged, 80 and over , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/therapeutic use , Cohort Studies , Dioxoles/adverse effects , Humans , Male , Middle Aged , Neoplasm Metastasis , Orchiectomy , Prostatic Neoplasms/pathology , Prostatic Neoplasms/surgery , Sarcoma/pathology , Sarcoma/surgery , Tetrahydroisoquinolines/adverse effects , Trabectedin , Treatment Failure , Treatment Outcome
4.
An. sist. sanit. Navar ; 34(3): 443-452, sept.-dic. 2011. tab
Article in Spanish | IBECS | ID: ibc-96220

ABSTRACT

Dada la diversidad de cuestionarios empleados en el estudio de la epidemiología analítica de las lesiones por tráfico, realizamos una revisión de los estudios publicados al respecto entre 1989 a 2011, con objeto de identificar sus fortalezas y debilidades. Dicha revisión puso de relieve que la mayor parte de los cuestionarios se centran en el factor humano sobre el riesgo de accidente, pero son muy pocos los que incluyen la intensidad de exposición y la asociación de ésta con otros factores de riesgo de la accidentalidad. Muchos cuestionarios poseen un elevado número de ítems y complejas escalas de valoración. Además, en España son escasos los cuestionarios validados sobre la exposición y la accidentalidad por tráfico. Por todo ello, es necesario trabajar en el diseño y la validación de cuestionarios que recojan de forma sencilla información integral sobre la epidemiología de las lesiones por tráfico de cara a su mayor conocimiento y prevención (AU)


Given the diversity of questionnaires currently being used in the study of the analytic epidemiology of traffic injuries, we made a review of studies on this question published between 1989 and 2011 in order toidentify their advantages and disadvantages. We wereable to observe that most of the questionnaires were focused on the human factor regarding the risk of road crashes, but very few of them included intensity of exposure and its association with other risk factors in road crashes. Many questionnaires have a high number of items and complex rating scales. Further more, in Spain there are few validated questionnaires which contain complete information about exposure and road crashes. In Spain we should work on the design and validation of questionnaires containing questions aimedat obtaining complete and easy information about the epidemiology of traffic injuries. In this way we would be able to increase our awareness of traffic injuries and how to prevent them (AU)


Subject(s)
Humans , Accidents, Traffic/trends , Risk-Taking , Automobile Driving/psychology , Risk Factors , Surveys and Questionnaires , Data Collection/methods , Risk Reduction Behavior
5.
Environ Toxicol ; 19(3): 241-9, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15101039

ABSTRACT

The quality control of wastewater treatments was monitored using selected novel and classical physicochemical and microbiological indicators, and the associations of the treatments with the effluents was analyzed. The microbiological indicators monitored were heterotrophic plate count (HPC), total coliforms (TC), fecal coliforms (FC), fecal streptococci (FS), sulfite-reducing clostridia (SRC), Pseudomonas aeruginosa, and Salmonella spp. The stages of wastewater treatment also were evaluated through determination of ammonia; biological oxygen demand (BOD(5)); chemical oxygen demand (COD); chloride; conductivity; suspended dissolved and total solids; fats; nitrate, nitrite, and total nitrogen; pH; phosphate and total phosphorus. Additional indicators included the Escherichia coli growth inhibition (IGEC) bioassay for assessing whole effluent toxicity, spectral determinations between wavelengths (lambda) 190-650 nm, and total (TP) and soluble (SP) protein contents. Of the more common physicochemical parameters, only BOD(5), COD, suspended and total solids, and fats showed a statistically significant reduction between raw water and effluent; for the microbiological indicators, significant reduction was seen only for HPC, FC, and Ps. aeruginosa. We suggest that determinations of Ps. aeruginosa be commonly used as an indicator of wastewater quality. Spectral analysis--most notably the values of absorbance at 225, 255, and 295 nm-revealed a statistically significant correlation with several physicochemical parameters. Statistical analysis of SP and TP values showed them to be good indicators of contamination. The quantitative study of Salmonella spp. and the results of the IGEC bioassay show the need for close control of infectious and toxic risks in wastewater and effluents.


Subject(s)
Sewage/chemistry , Sewage/microbiology , Waste Disposal, Fluid/standards , Water Microbiology , Water/standards , Bacteria/growth & development , Bacteria/isolation & purification , Biological Assay/methods , Colony Count, Microbial , Electric Conductivity , Escherichia coli/growth & development , Fats/analysis , Fats/standards , Hydrogen-Ion Concentration , Linear Models , Nitrogen/analysis , Nitrogen/standards , Oxygen/standards , Phosphorus/analysis , Phosphorus/standards , Proteins/analysis , Proteins/standards , Quality Control , Sewage/analysis , Spain , Spectrophotometry, Ultraviolet/statistics & numerical data , Toxicity Tests , Waste Disposal, Fluid/statistics & numerical data , Water/analysis , Water/chemistry , Water Microbiology/standards
6.
J Appl Toxicol ; 22(6): 353-7, 2002.
Article in English | MEDLINE | ID: mdl-12424739

ABSTRACT

Dithiocarbamates (DTCs) are chemicals featuring a great chelating capacity. The toxicological study of DTCs is very important in view of their relatively simple synthesis and wide array of sanitary and industrial applications. In this study, the toxicity of some of the more recently synthesized DTCs is determined using an extremely simple bioassay, described in previous studies, based on the inhibition of growth of Escherichia coli (IGEC). The lowest-observed-effect concentration (LOEC), the median effective concentration (EC(50)) and no-observed-effect concentration (NOEC) of the following sodium dithiocarbamates was determined: N-benzyl-N-methyldithiocarbamate x 2H(2)O, N-benzyl-N-isopropyldithiocarbamate x 3H(2)O, N-benzyl-N-ethyldithiocarbamate x 2H(2)O, N-butyl-N-methyldithiocarbamate x 2H(2)O, N,N-dibenzyldithiocarbamate x 2H(2)O and N-benzyl-2-phenethyldithiocarbamate x 4H(2)O. Our results showed N,N-dibenzyl-DTC to be the least toxic of the tested substances, with an EC(50) value of 1,269.9 micro g ml(-1), whereas N-butyl-N-methyl-DTC and N-benzyl-N-methyl-DTC, with respective EC(50) values of 14.9 micro g ml(-1) and 23.5 micro g ml(-1), were the most toxic. Regression analysis showed, through exponential models, that the degree of toxicity of this group of substances correlated with the molecular weight of the compound, the molecular weight of the smallest chemical radical linked to the dithiocarbamate group and the number of benzene rings present in the molecule. The consideration of these models allows us to establish that in general terms the toxicity of DTCs decreases exponentially with a greater molecular weight and the number of benzene rings.


Subject(s)
Chelating Agents/toxicity , Thiocarbamates/toxicity , Biological Assay , Chelating Agents/chemical synthesis , Chelating Agents/chemistry , Escherichia coli/drug effects , Escherichia coli/growth & development , Molecular Structure , Molecular Weight , Quantitative Structure-Activity Relationship , Thiocarbamates/chemical synthesis , Thiocarbamates/chemistry
7.
J Epidemiol Community Health ; 54(7): 544-51, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10846198

ABSTRACT

STUDY OBJECTIVE: To assess the validity and factors related with the validity of self reported numbers of visits to a primary health care centre, in comparison with the recorded number. DESIGN: Cross sectional study. SETTING: The urban area served by the Zaidín-Sur Primary Health Care Centre (Granada, Spain). PARTICIPANTS: Two population samples (236 high users and 420 normal users) who were seen at the centre from 1985 to 1991 were interviewed in 1993. MAIN RESULTS: A net tendency to overreport the actual number of visits was observed. Absolute concordance between self reported and recorded utilisation decreased as time interval lengthened, although this mainly reflected the increase in maximum variability both with time interval length and with the number of recorded visits. Corrected Spearman rho coefficients obtained between the number of self reported and recorded visits ranged from 0.602 for the two weeks before the interview to 0.678 for the year before. Regression slopes of self reported utilisation upon recorded utilisation did not change between periods. In multiple regression analyses the actual number of visits was the main factor associated with both underreporting and overreporting. Older age was also significantly associated with underreporting. Poor health status and high satisfaction with health care were significantly associated with overreporting. CONCLUSIONS: There was a substantial degree of inaccuracy in self reported utilisation, with a net tendency to overreport the number of visits. In relative terms, however, accuracy of self reports did not seem to decrease appreciably as the recall time lengthened. To compare the accuracy of different measures, it is important to take into account the maximum variability of each one. Otherwise, contradictory results may be obtained.


Subject(s)
Attitude to Health , Primary Health Care/statistics & numerical data , Adolescent , Adult , Aged , Cross-Sectional Studies , Data Interpretation, Statistical , Female , Health Status , Humans , Male , Middle Aged , Reproducibility of Results , Spain , Statistics, Nonparametric
8.
Psychol Med ; 29(6): 1347-57, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10616940

ABSTRACT

BACKGROUND: The reasons for high use of primary care, and in particular the role of psychosocial factors, remain unclear. METHODS: We identified and interviewed 236 frequent attenders and 420 normal users, matched by age and sex, of a public Health Centre in Granada, Spain. Users were questioned about mental health (GHQ-28), social support (Duke-UNC-11), family dysfunction (family APGAR) and health beliefs (health belief model, locus of health control and medical care expectations). We also measured a set of individual, social and illness variables. RESULTS: Multiple logistic regression analyses showed that mental health was the main factor associated with frequent attender status (odds ratio = 3.1; 2.4-3.9). The association was stronger than that between frequent attender status and perceived illness, and between the former and reported chronic illness. Family dysfunction and perceived susceptibility to and severity of disease were also significantly but more weakly associated with frequent attender status. Affective support was more strongly associated with FA status than was confidant support, but both associations disappeared when mental health and family function were controlled for. CONCLUSIONS: Our findings document the association of psychosocial factors and primary health care use. We suggest that the effective management of mental health problems from a family-based approach may reduce primary health care high use.


Subject(s)
Chronic Disease/psychology , Health Services Misuse/statistics & numerical data , Primary Health Care/statistics & numerical data , Sick Role , Adolescent , Adult , Aged , Chronic Disease/epidemiology , Cross-Sectional Studies , Family Relations , Female , Humans , Internal-External Control , Male , Mental Disorders/diagnosis , Mental Disorders/psychology , Middle Aged , Personality Inventory , Social Support , Spain
9.
Int J Tuberc Lung Dis ; 2(1): 62-8, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9562113

ABSTRACT

SETTING: Among the cytokines involved in defensive mechanisms against Mycobacterium tuberculosis infection, special attention has been given to interferon-gamma (IFN-gamma); a local synthesis of this cytokine as well as IL-2 (type 1 cytokines) at the site of disease in patients with tuberculous pleuritis has been demonstrated. Moreover, high levels of IgG autoantibodies against IFN-gamma have been shown in several clinical situations. It has been suggested that these antibodies could serve to limit the intensity or duration of the immune response or be able to interfere with the pathophysiological effects of IFN-gamma. OBJECTIVE: To investigate the potential role of anti-IFN-gamma antibodies in the course of M. tuberculosis infection. DESIGN: Investigation of the presence of these antibodies in sera from healthy and ill subjects infected with M. tuberculosis in relation to the extent of the disease and the presence of IFN-gamma in sera by enzyme-linked-immunosorbent assay (ELISA). In order to investigate the presence of these antibodies at the site of infection we included 12 pleural fluids from tuberculosis patients and 9 pleural fluids from other origins. RESULTS: In the course of M. tuberculosis infection the production of anti-IFN-gamma IgG antibodies is induced, being particularly higher in healthy skin test converters. Among tuberculosis patients, the presence of anti-IFN-gamma autoantibodies is significantly associated with detectable levels of the cytokine in sera. Levels of anti-IFN-gamma antibodies in moderately advanced and far advanced tuberculosis patients are significantly greater than in healthy individuals. These antibodies increase at the site of infection. CONCLUSION: Anti-IFN-gamma antibodies must be considered as a new element in the immune response to M. tuberculosis. It would be of great interest to investigate this point especially at the site of infection.


Subject(s)
Autoantibodies/analysis , Interferon-gamma/immunology , Mycobacterium tuberculosis/immunology , Tuberculosis, Pulmonary/immunology , Antibody Specificity , Autoantibodies/blood , Autoantibodies/immunology , Blotting, Western , Chi-Square Distribution , Enzyme-Linked Immunosorbent Assay , Humans , Immunoglobulin G/analysis , Immunoglobulin G/blood , Immunoglobulin G/immunology , Interferon-gamma/biosynthesis , Interferon-gamma/blood , Interleukin-2/biosynthesis , Pleural Effusion/immunology , Skin/immunology , Tuberculin Test , Tuberculosis, Pleural/immunology , Tuberculosis, Pulmonary/blood
10.
Mol Cell Biol ; 16(10): 5386-92, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8816450

ABSTRACT

Three subtypes of retinoic acid receptors (RAR), termed RAR alpha, RAR beta, and RAR gamma, have been described. They are composed of different structural domains, including distinct domains for DNA and ligand binding. RARs specifically bind all-trans-retinoic acid (RA), 9-cis-RA, and retinoid analogs. In this study, we examined the functional role of cysteine and arginine residues in the ligand-binding domain of hRAR alpha (hRAR alpha-LBD, amino acids 154 to 462). All conserved cysteine and arginine residues in this domain were mutated by site-directed mutagenesis, and the mutant proteins were characterized by blocking reactions, ligand-binding experiments, transactivation assays, and protease mapping. Changes of any cysteine residue of the hRAR alpha-LBD had no significant influence on the binding of all-trans RA or 9-cis RA. Interestingly, residue C-235 is specifically important in antagonist binding. With respect to arginine residues, only the two single mutations of R-276 and R-394 to alanine showed a dramatic decrease of agonist and antagonist binding whereas the R272A mutation showed only a slight effect. For all other arginine mutations, no differences in affinity were detectable. The two mutations R217A and R294A caused an increased binding efficiency for antagonists but no change in agonist binding. From these results, we can conclude that electrostatic interactions of retinoids with the RAR alpha-LBD play a significant role in ligand binding. In addition, antagonists show distinctly different requirements for efficient binding, which may contribute to their interference in the ligand-inducible transactivation function of RAR alpha.


Subject(s)
Receptors, Retinoic Acid/chemistry , Receptors, Retinoic Acid/metabolism , Tretinoin/metabolism , Alanine , Amino Acid Sequence , Animals , Arginine , Base Sequence , Benzoates/metabolism , Binding Sites , Chromans/metabolism , Cysteine , Humans , Kinetics , Ligands , Molecular Sequence Data , Mutagenesis, Site-Directed , Oligodeoxyribonucleotides , Point Mutation , Protein Biosynthesis , Rabbits , Reticulocytes/metabolism , Retinoic Acid Receptor alpha , Retinoids/metabolism , Sequence Homology, Amino Acid , Transcription, Genetic , Transcriptional Activation , Retinoic Acid Receptor gamma
11.
Eur J Clin Microbiol Infect Dis ; 14(7): 591-6, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7588843

ABSTRACT

To investigate the association of human immunodeficiency virus (HIV) with various DNA viruses, including hepatitis B virus (HBV), cytomegalovirus (CMV) and Epstein-Barr virus, (EBV), simultaneous detection of HIV p24 antigen, HBV surface antigen and DNA, CMV-DNA and EBV-DNA expression was performed in phytohemagglutinin-stimulated peripheral blood mononuclear (PBMC) culture supernatants obtained from 54 individuals at risk for HIV infection. HIV expression in PBMC culture supernatants never occurred alone; expression of other viruses was always detected in the 24 samples expressing HIV antigen in vitro. Furthermore, in 16 patients expression of other viruses was detected without HIV expression, and in 14 patients none of the tested viruses were detected. These results indicate a strong association between the presence of HIV antibody and expression of DNA viruses in vitro (p = 0.0001). The coexpression of these viruses could be related to the evolution of HIV infection and AIDS.


Subject(s)
Cytomegalovirus/isolation & purification , HIV Infections/virology , Hepatitis B virus/isolation & purification , Herpesvirus 4, Human/isolation & purification , Cells, Cultured , Cytomegalovirus/genetics , Cytomegalovirus/immunology , DNA, Viral/analysis , HIV Core Protein p24/analysis , Hepatitis B virus/genetics , Hepatitis B virus/immunology , Herpesvirus 4, Human/genetics , Herpesvirus 4, Human/immunology , Humans , Leukocytes, Mononuclear/virology
12.
Int J Addict ; 29(14): 1893-907, 1994 Dec.
Article in English | MEDLINE | ID: mdl-7890447

ABSTRACT

This article examines the relationship between sharing and sexual behavior in a nationwide sample of 1,074 intravenous drug users (IVDUs) in ambulatory treatment in Spain. Of our sample, 31.9% shared or had shared injecting equipment. Sharing was associated with sex-less frequent in males--and yielded an inverse relationship with age, years of education, and age at first intravenous drug use. Sharers, especially women, engaged more frequently in sex in exchange for money. A small proportion (6.3%) of male IVDUs had bisexual or homosexual relations. Condoms were always used by 18.4% of males and 15.9% of females. The sharing of injecting equipment was not generally associated with a particular type of penetrative sexual encounter, although condom use was less frequent among IVDUs who shared injecting equipment. The limitations of the present study are discussed.


Subject(s)
Needle Sharing/statistics & numerical data , Sexual Behavior , Substance Abuse, Intravenous/epidemiology , Adult , Ambulatory Care/statistics & numerical data , Condoms/statistics & numerical data , Cross-Sectional Studies , Female , Homosexuality, Male/statistics & numerical data , Humans , Incidence , Male , Opioid-Related Disorders/epidemiology , Opioid-Related Disorders/rehabilitation , Spain/epidemiology , Substance Abuse, Intravenous/rehabilitation
13.
Clin Investig ; 72(11): 853-7, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7894211

ABSTRACT

We analyzed the association between hyperandrogenism and hyperinsulinemia, and their relationship to body mass index, in a large series of patients with polycystic ovary syndrome (PCOS). A characteristic hormonal profile was sought in women with marked hyperinsulinemia. The patient group consisted of 73 women with PCOS, ranging in age from 16 to 29 years. The control group consisted of 34 healthy women with no evidence of hyperandrogenism, aged 19-30 years. None of the patients or control women had a body mass index above 27 kg/m2. Follicle-stimulating hormone, luteinizing hormone, prolactin, testosterone, estradiol, androstenedione, dehydroepiandrosterone sulfate, sex hormone binding globulin, 17-hydroxyprogesterone, and free cortisol were determined by radioimmunoassay. The free testosterone index was calculated. The oral glucose tolerance test was used to analyze basal insulinemia, maximum insulin peak, and the insulinemia/glycemia index. In the group with PCOS body mass index was greater, free testosterone index was higher, and levels of dehydroepiandrosterone sulfate, testosterone, 17-hydroxyprogesterone (P < 0.001) and androstenedione (P < 0.05) were higher than in the control group. Of the insulin parameters, basal insulinemia, maximum insulin peak, and insulinemia/glycemia index were higher in the patient group (P < 0.001). In patients with marked insulinemia, free testosterone index was more markedly elevated, and gonadotrophin levels were normal. Our data confirm that a characteristic pattern of hyperinsulinemia is associated with PCOS. We found no causal relationship between hyperinsulinemia and androgen levels. A characteristic hormonal pattern was found in patients with marked hyperinsulinemia.


Subject(s)
Androgens/blood , Body Mass Index , Insulin/blood , Polycystic Ovary Syndrome/blood , Adolescent , Adult , Female , Humans , Male , Statistics as Topic
14.
J Epidemiol Community Health ; 48(5): 459-63, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7964355

ABSTRACT

STUDY OBJECTIVE: To determine whether HIV positive intravenous drug users (IVDUs) who were receiving outpatient treatment for opiate and cocaine abuse or dependence used practices aimed at reducing the spread of HIV. DESIGN: Cross sectional study of behaviour and HIV serostatus in IVDUs. SETTING: A nationwide sample, from 83 health centres for outpatient treatment, stratified by autonomous regions. PARTICIPANTS: Altogether 1074 IVDUs were recruited. HIV serostatus could be verified in 738 (68.7%) of these. MEASUREMENTS AND MAIN RESULTS: Crude and adjusted odds ratios and their 95% confidence intervals were estimated to assess the association between HIV serostatus and behavioural changes. In their daily interactions with other members of the same household, seropositive subjects more frequently used preventive methods aimed at avoiding transmission than seronegative patients. Treatment for abuse or dependency before the current regimen had a greater impact in HIV positive than HIV negative subjects in terms of abstaining from risk behaviours. There was a significant trend toward lower drug consumption in HIV positive subjects, and the number of seropositive and seronegative IVDUs who stopped injecting their drugs was significantly higher among the former. Seropositive subjects were also more likely to stop sharing drug injecting equipment and to change their sexual habits; they reported an increased consistent use of condoms. CONCLUSIONS: HIV positive IVDUs were more likely to change their risk behaviours than their HIV negative counterparts.


Subject(s)
HIV Seropositivity/psychology , Risk-Taking , Substance Abuse, Intravenous/psychology , Adolescent , Adult , Cross-Sectional Studies , Female , HIV Infections/prevention & control , HIV Infections/transmission , Humans , Illicit Drugs , Male , Middle Aged , Sexual Behavior , Spain
15.
J Endocrinol Invest ; 17(8): 647-52, 1994 Sep.
Article in English | MEDLINE | ID: mdl-7868804

ABSTRACT

Several different strategies were used to investigate the relationship between hyperandrogenism and hyperinsulinemia associated with polycystic ovary syndrome. Ketoconazole was given orally (400 mg/day) for 9 months to evaluate the effect of reduction in ovarian and adrenal androgens on insulin response (oral glucose tolerance test) in 35 women with polycystic ovary syndrome. Androgenic steroids (testosterone, androstenedione, dehydroepiandrosterone sulphate, and free testosterone index) decreased (p < 0.01), but basal insulinemia, maximum peak insulin, and insulin/glucose ratio showed no significant changes. One month after treatment was stopped, free testosterone index, and serum concentrations of androstenedione and testosterone, increased (p < 0.05), but no alterations were noted in insulin parameters. Body mass index was stable throughout the ten-month study period. Our findings suggest that endogenous androgens, no matter whether they are of ovarian or adrenal origin, do not play a major role in the modulation of hyperinsulinemia in patients with polycystic ovary syndrome.


Subject(s)
Androgens/blood , Insulin/blood , Ketoconazole/administration & dosage , Polycystic Ovary Syndrome/blood , Adolescent , Adult , Drug Administration Schedule , Female , Humans , Statistics as Topic , Time Factors
16.
Int J Epidemiol ; 23(4): 805-11, 1994 Aug.
Article in English | MEDLINE | ID: mdl-8002195

ABSTRACT

BACKGROUND: Of critical importance to AIDS control in Spain is the analysis of geographical variation and trend over time in the prevalence of intravenous administration in heroin users, as well as the factors associated with the use of this route. METHODS: We carried out a cross-sectional study of 27,655 people admitted to outpatient treatment for heroin dependence in 15 of the 17 Autonomous Communities of Spain during 1991, using data provided by the State Information System on Drug Abuse (SEIT). To assess the association of some factors with use of the intravenous route crude and logistic analysis was performed. RESULTS: The prevalence of intravenous administration in this population was 64.4% with regional differences ranging between 33% and 90%. Crude and logistic analysis demonstrated a strong association with two factors in addition to geography: the year of first use and the age at first use (the earlier the first use, the greater the strength of the association). CONCLUSIONS: These findings are of paramount importance for the control of the HIV epidemic in Spain and further study in this area could help to guide policy development.


Subject(s)
Heroin Dependence/epidemiology , Population Surveillance , Substance Abuse, Intravenous/epidemiology , Acquired Immunodeficiency Syndrome/etiology , Acquired Immunodeficiency Syndrome/prevention & control , Adolescent , Adult , Age Factors , Ambulatory Care , Cross-Sectional Studies , Female , Heroin Dependence/complications , Heroin Dependence/therapy , Humans , Logistic Models , Male , Prevalence , Residence Characteristics , Risk Factors , Spain/epidemiology , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/therapy , Time Factors
17.
Exp Toxicol Pathol ; 46(2): 95-100, 1994 Jul.
Article in English | MEDLINE | ID: mdl-7987078

ABSTRACT

The proliferation rate in livers of 120 mice (60 males and 60 females) was analyzed by immunohistochemical detection of bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression on ethanol-fixed/paraffin-embedded specimens. Mice were divided into three groups, with 20 males and 20 females in each group: mice in the first group served as controls, while mice in the second and third groups were treated with a low and a high dose, respectively, of a non-genotoxic drug candidate for 2 weeks. A dose-related increase of the proliferating hepatocyte fraction was disclosed by both immunohistochemical methods, reaching statistical significance already in the low-dose male group for BrdU incorporation and in both male and female low-dose groups for PCNA expression. A good correlation between the degree of BrdU and PCNA labeling was observed and, as expected, the percentage of PCNA expressing cells was generally higher than the percentage of BrdU-positive cells. We concluded that the detection of PCNA expression represents a reliable method for the quantification of the hepatocytic proliferating fraction in rodents and allows the use of archival material for cell kinetic investigations in toxicologic pathology.


Subject(s)
Bromodeoxyuridine/analysis , Cell Division/physiology , Liver/chemistry , Liver/cytology , Proliferating Cell Nuclear Antigen/analysis , Animals , Antibodies, Monoclonal , Female , Immunoenzyme Techniques , Liver/pathology , Male , Mice , Mice, Inbred Strains , Toxicology/methods
20.
Eur J Endocrinol ; 130(4): 333-8, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8162160

ABSTRACT

The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome. The study group comprised 37 women with signs of hyperandrogenism (hirsutism, acne) and oligomenorrhea. A low dose (400 mg/day) of ketoconazole was tested in a 9-month prospective clinical study. Clinical response (Ferriman & Gallway score, acne) and modifications in hormone pattern (luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, prolactin, 17-hydroxy-progesterone, androstenedione, steroid hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, adrenocorticotropin (ACTH) and free testesterone index) were measured, and ACTH stimulation tests were performed. Tolerance and side-effect also were assessed. After 9 months of ketoconazole treatment, the patients' Ferriman & Gallway scores (18.26 +/- 4.6 vs 12.4 +/- 4.1; p < 0.001) and acne had improved markedly. Hormone patterns also became more favorable, with decreases in androgenic steroids (testosterone, androstenedione, free testosterone index and dehydroepiandrosterone sulfate; p < 0.01) and increases in estradiol (p < 0.01). Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly, remaining within the reference range. Increases in ACTH were observed only in the 3rd month (p < 0.01). Initial levels of androgenic steroids were correlated inversely with their percentage decrease in successive samplings. Decreases in adrenal androgenic steroids were associated with an increase in steroid hormone-binding globulin. The side-effects of treatment, although not severe, caused some discomfort and led to a high drop-out rate (30%).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Hyperandrogenism/drug therapy , Ketoconazole/therapeutic use , Acne Vulgaris , Adolescent , Adult , Female , Follicle Stimulating Hormone/blood , Gonadal Steroid Hormones/blood , Hirsutism , Humans , Hydrocortisone/blood , Hyperandrogenism/metabolism , Ketoconazole/adverse effects , Liver/drug effects , Liver/enzymology , Luteinizing Hormone/blood , Oligomenorrhea , Prospective Studies , Transaminases/blood
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