Human papillomavirus infection in Honduran women with normal cytology.

OBJECTIVE: This study was aimed at estimating type-specific HPV prevalence and its cofactors among Honduran women with normal cytology in order to provide valuable information to health policymakers about the epidemiology of this important sexually transmitted infection. METHODS: A total of 591 women with normal cytology from Tegucigalpa, Honduras were interviewed and tested for HPV using the SPF10 LiPA25. A structured epidemiological questionnaire was administered to each woman. RESULTS: The overall HPV prevalence was 51%. Twenty-three types of HPV were detected; HPV 16, 51, 31, 18, and 11 were the most common. The highest prevalence of cancer associated HPV types (15.0%) was found in the women less than 35 years. Besides the association with age, the main independent predictors of HPV infection were the lifetime number of sexual partners and having a low socioeconomic status and less than 5 previous Pap smears. CONCLUSIONS: In the population studied, there was a broad diversity of HPV infections, with high-risk types being the most common types detected. The establishment of a well-characterized population with regard to the community prevalence of type-specific HPV infection will provide a valuable baseline for monitoring population effectiveness of an HPV vaccine.

Sublingual immunotherapy provides an early increase of interferon-gamma production.

Allergic rhinitis (AR) is characterized by Th2 polarized immune response. Allergen-specific subcutaneous immunotherapy may restore a physiologic Th1 profile. However, there are few studies investigating the immunological effects of sublingual immunotherapy (SLIT). The aim of this study is to investigate whether a pre-seasonal SLIT course could affect IFN-gamma production. Forty-four AR patients with pollen allergy assumed pre-seasonal SLIT for 3 months. IFN-gamma-specific producing cells were assessed by cytokine ELISPOT before and 3 months after the beginning of SLIT. Visual analogue scale (VAS) for symptoms and medication score was also evaluated. The frequency of IFN-gamma-specific producing cells significantly increased after SLIT (p<0.01), and this increase was significantly associated with improvement of both symptoms (p<0.001) and medication use (p<0.01). In conclusion, these results may be considered clinically relevant as SLIT treatment may induce a quick IFN- gamma response that is related to clinical improvement.

Safety and immunogenicity of two influenza virus subunit vaccines, with or without MF59 adjuvant, administered to human immunodeficiency virus type 1-seropositive and -seronegative adults.

The objective of this study was to evaluate and compare both the safety and tolerability and the humoral and cell-mediated immune responses for two influenza virus subunit vaccines, one with MF59 adjuvant (Fluad) and one without an adjuvant (Agrippal), in healthy and in human immunodeficiency virus type 1 (HIV-1)-infected adult individuals. To achieve this aim, an open, randomized, comparative clinical trial was performed during the 2005-2006 season. A total of 256 subjects were enrolled to receive one dose of vaccine intramuscularly. Blood samples were taken at the time of vaccination and at 1 and 3 months postvaccination. A good humoral antibody response was detected for both vaccines, meeting all the criteria of the Committee for Medical Products for Human Use. After Beyer's correction for prevaccination status, Fluad exhibited better immunogenicity than Agrippal, as shown from the analysis of the geometric mean titers, with significant differences for some virus strains; however, no definitive conclusions on the clinical significance of such results can be drawn, because the method used to estimate antibody response is currently nonstandard for influenza virus vaccines. Significant induction of an antigen-specific CD4+ T-lymphocyte proliferative response was detected at all time points after immunization, for both the vaccines, among HIV-1-seronegative subjects. This was different from what was observed for HIV-1-infected individuals. In this group, significance was not reached at 30 days postvaccination (T30) for those immunized with Agrippal. Also when data were compared between treatment groups, a clear difference in the response at T30 was observed in favor of Fluad (P = 0.0002). The safety profiles of both vaccines were excellent. For HIV-1-infected individuals, no significant changes either in viremia or in the CD4+ cell count were observed at any time point. The results showed good safety and immunogenicity for both vaccines under study for both uninfected and HIV-1-infected adults, confirming current recommendations for immunization of this high-risk category.

Self-overlap as a method of analysis in Ising models.

The damage spreading (DS) method provided a useful tool to obtain analytical results of the thermodynamics and stability of the two-dimensional (2D) Ising model--amongst many others--but it suffered both from ambiguities in its results and from large computational costs. In this paper we propose an alternative method, the so-called self-overlap method, based on the study of correlation functions measured at subsequent time steps as the system evolves towards its equilibrium. Applying Markovian and mean-field approximations to a 2D Ising system we obtain both analytical and numerical results on the thermodynamics that agree with the expected behavior. We also provide some analytical results on the stability of the system. Since only a single replica of the system needs to be studied, this method would seem to be free from the ambiguities that afflicted the DS method. It also seems to be numerically more efficient and analytically simpler.

Sublingual specific immunotherapy reduces PBMC proliferations.

BACKGROUND: Subcutaneous specific immunotherapy has been demonstrated capable of inducing T regulatory response. There is few evidence concerning immunological changes induced by sublingual immunotherapy. OBJECTIVE: The aim of this study was to evaluate T cell proliferation in subjects successfully treated with SLIT for HDM. METHODS: PBMCs were isolated from patients after at least 3 years of successful HDM SLIT and from matched untreated allergic and healthy control subjects. After 3 and 6 days of in vitro stimulation with PHA, Candida albicans, Dermatophagoides farinae, grasses, Parietaria judaica, and cat, proliferation. RESULTS: Subjects treated with SLIT showed significant reduction of proliferation induced by Candida albicans, Parietaria, and grasses in comparison with untreated atopics (p=0.0002, 0.0033, and 0.009 respectively). CONCLUSION: This pilot study confirms reduced T cell proliferation in allergic subjects treated with SLIT.

Neurilemomas de cavidad oral y cuello / Neurilemmomas of the oral cavity and the neck

Los neurilemomas son tumores neurogénicos benignos, con origen en la vaina neural. De los neurilemomas extracraneales, aproximadamente un 25 a un 45 por ciento ocurren en cabeza y cuello. La edad de afectación predominante es entre la tercera y la cuarta décadas de vida. El neurilemoma es un tumor claramente circunscrito y, generalmente, de pequeño tamaño. Clínicamente aparece como una masa de crecimiento lento y gradual. El examen microscópico es necesario para el diagnóstico. El tratamiento de elección es la escisión quirúrgica completa tumoral y después de ésta es muy rara su recurrencia.El propósito de este artículo es presentar un estudio retrospectivo, de nueve casos, de neurilemomas de cavidad oral y cuello, tratados en nuestro servicio de Cirugía Oral y Maxilofacial, entre 1997 y 2001. Hemos valorado una serie de parámetros epidemiológicos (edad, sexo, localización, tamaño, clínica, estudios previos a la cirugía, tiempo trascurrido entre aparición de síntomas y primera consulta, nervio de origen, patrón histológico predominante (Antoni A, Antoni B), y evolución postquirúrgica. Se ha realizado una revisión de la literatura (AU)

La evaluación de la calidad de vida relacionada con la salud en la consulta: las viñetas / Evaluation in the clinic of health-related quality of life: the COOP/WONCA cartoons

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Neuroendocrine effects of Hypericum extract WS 5570 in 12 healthy male volunteers.

In the present study, the effects of acute p.o. administration of placebo at 300 mg and 600 mg of WS 5570 Hypericum perforatum extract on cortisol (COR), growth hormone (GH) and prolactin (PRL) secretion were examined in twelve physically and mentally healthy subjects. WS 5570 is a hyperforin containing extract of St. John's Wort which has been proven effective in mild to moderate depression. After inserting an i.v. catheter, blood samples were drawn one hour prior to the administration of WS 5570 or placebo, at the time of application and up to five hours after application in 30-minute intervals. Plasma concentrations of COR, GH, and PRL were determined in each blood sample by double-antibody RIA methods. No PRL stimulation could be observed after placebo or after WS 5570 (300, 600 mg). A small but statistically significant elevation in GH AUC values occurred after 300 mg of WS 5570. After 600 mg of WS 5570, a clear-cut COR stimulation was observed, occurring from 30 up to 90 minutes after the application. In this period of time (from t = 30 min to t = 90 min), the mean COR concentrations were significantly higher after 600 mg of WS 5570 compared to placebo. 300 mg of WS 5570 did not show any effects on COR secretion. We propose that the Hypericum extract WS 5570 is able to influence central neurotransmitters, thereby causing COR stimulation in a dose-dependent manner.

Co-factors related to the causal relationship between human papillomavirus and invasive cervical cancer in Honduras.

BACKGROUND: A case-control study was conducted in Honduras to identify co-factors in the carcinogenic pathway by which human papillomavirus (HPV) causes invasive cervical cancer. METHODS: Ninety-nine cases aged 23-65 (median 47) years participated. Two controls were matched to each case by age and clinic where they first presented for cytological screening; controls had no cervical abnormalities. Information on risk factors was obtained by personal interviews in the clinics regarding sociodemographic, reproductive and behavioral characteristics. Human papillomavirus was detected in cervical scrapes by general primer-mediated polymerase chain reaction (PCR) followed by sequence analysis to identify the different types present. RESULTS: All cases had squamous cell tumours and most were FIGO (International Federation of Gynecologists and Obstetricians) class II or higher; HPV was strongly associated with cervical cancer (odds ratio [OR] = 7.66, 95% CI : 3.88-15.1). Among HPV-positive women, dose-response relationships were observed for education, age at first intercourse and exposure to wood smoke that persisted after adjustment for previous screening. Among HPV-negative women, the number of sexual partners and parity were associated with cervical cancer. The protective effect of previous cytological screening operated independently of HPV. CONCLUSIONS: Our findings speak for the powerful role that both primary and secondary education plays in fostering a lifestyle that reduces the risk of invasive cervical cancer. The data suggest that important elements of such a lifestyle include later age at first sexual intercourse, a limited number of pregnancies, greater likelihood of undergoing cytological screening and reduced exposure to carcinogens in the household environment.

Human papillomavirus infection, cervical dysplasia and invasive cervical cancer in Honduras: a case-control study.

A substantial body of evidence has confirmed human papillomavirus (HPV) infection as the central etiological agent in human cervical carcinogenesis. In Honduras, cervical cancer is the most common cancer among women, with a high annual incidence. We conducted a population-based, case-control study of 229 patients with different grades of CIN and invasive cervical cancer and 438 matched controls. A structured questionnaire was used to investigate known and probable risk factors for cervical cancer. Cervical scrapes were tested for the presence of different HPV types using a general primer-mediated PCR followed by PCR-based sequencing. HPV DNA was detected in 87% of all cancer in situ and invasive cancer cases, and 95% of invasive cases could be attributed to high-risk types. In control women, 39% were positive for HPV DNA sequences. HPV 16 prevalence ranked highest in all stages of cervical dysplasias, invasive cancers and controls. A statistically significant association with HPV was observed for CIN II, CIN III and invasive cancer, showing an upward trend to more severe lesions and being more pronounced for HPV 16 and related types. The OR for HPV 16- and 18-related invasive cancer cases was 14.88 (95% CI 5.12-43.25) and 74.66 (95% CI 7.77-717.62), respectively. Our results confirm a central role of HPV as the cause of cervical cancer in Honduras and provide information as to the type distribution of HPVs in the country.

HLA DOA1 and DOB1 loci in Honduran women with cervical dysplasia and invasive cervical carcinoma and their relationship to human papillomavirus infection.

Molecular and epidemiological studies have demonstrated that certain types of human papillomavirus (HPV), mainly HPV-16 and HPV-18, are the primary causes of cervical cancer and its precursor lesions; there is now evidence for a clear association with specific HLA class I and class II loci contributing independently to the expression of cervical cancer. Among Honduran women carcinoma of the cervix is the most common type of cancer, and infections with high-risk HPV types are highly prevalent. To study the interactive role of viral-host genetics, we performed PCR amplification of DNA and sequence-specific oligonucleotide probe typing on cervical scrapes from 49 women [24 with cervical intraepithelial neoplasia stage III or cervical cancer (severe cases) and 25 with stage I or II cervical intraepithelial neoplasia (mild cases)] and 75 control subjects to look for possible associations between HPV and HLA class II DQA1 and DQB1 alleles in the development of dysplasias and invasive cancer. This analysis revealed a predominance of HLA-DQA1*0301 among severe-case patients [relative risk (RR) = 3.45, p = 0.008), whereas DQA1*0501 was negatively associated (RR = 0.30, p = 0.03), suggesting a protective effect of this allele. HPV typing showed a decreased relative risk among the HPV-16 or HPV-18 carrying patients and other HPV-related positive patients in the presence of DQB1*0602 compared with positive control subjects (p = 0.04). No statistically significant allele frequency difference was observed between mild dysplasia cases and control subjects. The results suggest that DQA1*03011, which is in linkage desequilibrium with all HLA-DR4 alleles, confers an increased risk for severe cervical dysplasia and invasive cancer, whereas DQA1*0501, which is in several DR52 haplotypes, has a protective effect. Furthermore, specific HLA-DQB1 sequences may be important in determining the immune response to HPV peptides and may affect the risk for cervical cancer after HPV infection in mestizo Honduran women.

Modulation of the insulin-like growth factor-I system by N-(4-hydroxyphenyl)-retinamide in human breast cancer cell lines.

The potent mitogenic activity of insulin-like growth factor I (IGF-I) on breast epithelium is inhibited by retinoic acid in oestrogen receptor-positive (ER+) breast cancer cell lines. We studied and compared the effects of N-(4-hydroxyphenyl)-retinamide (4-HPR) in terms of growth inhibition and modulation of the IGF-I system in ER+ (MCF-7) and oestrogen receptor-negative (ER-) (MDA-MB231) breast cancer cell lines. Treatment with 1-10 microM 4-HPR for up to 96 h induced a dose- and time-dependent inhibition of proliferation in both breast cancer cell lines. Induction of apoptosis was much more evident in MCF-7 than in MDA-MB231 cells (30-40% compared with 0-5% respectively at 5 microM for 48 h). Exogenous human recombinant IGF-I (hr-IGF-I)-stimulated cell proliferation was abolished by 1 microM 4-HPR in MCF-7 cells. Immunoreactive IGF-I-like protein concentration in conditioned medium was reduced by 38% in MCF-7 and by 90% in MDA-MB231 cell lines following treatment for 48 h with 5 microM 4-HPR. Western ligand blot analysis showed a reduction of IGF-binding protein 4 (BP4) and BP5 by 67% and 87%, respectively, in MCF-7, whereas IGF-BP4 and -BP1 were reduced by approximately 20% in MDA-MB231 cells. Exposure to 5 microM 4-HPR for 48 h inhibited [125I]IGF-I binding and Scatchard analysis revealed a decrease of more than 50% in maximum binding capacity (Bmax) and a reduced receptor number/cell in both cancer cell lines. Steady-state type I IGF-receptor mRNA levels were reduced by approximately 30% in both tumour cell lines. We conclude that 4-HPR induces a significant down-regulation of the IGF-I system in both ER+ (MCF-7) and ER- (MDA-MB231) breast cancer cell lines. These findings suggest that, in our model, interference with the ER signalling pathway is not the only mechanism of breast cancer growth inhibition by 4-HPR.

A sero-epidemiological study of the relationship between sexually transmitted agents and cervical cancer in Honduras.

To investigate a possible cause-and-effect relationship between sexually transmitted diseases and cervical cancer, we performed a sero-epidemiological study on the presence of antibodies against a number of sexually transmitted agents (STAs) in patients with cervical cancer and their matched controls. In this study, we used serological techniques to investigate the presence of antibodies to cytomegalovirus, herpes simplex virus type 2, human immunodeficiency virus, Chlamydia trachomatis, Treponema pallidum and human papillomavirus (HPV) early protein E7 in sera from patients with cervical cancer, cervical intra-epithelial neoplasia and individually matched, healthy controls. The presence of antibodies to infectious agents other than HPV appeared not to be associated with risk of cervical neoplasia in either univariate or multivariate analysis. After adjustment for cytology, schooling and presence of HPV DNA in cervical scrapes, there was a significantly higher prevalence of antibodies to HPV-16 E7 protein in sera from patients with cervical cancer (OR = 3.6, 95% CI 1.0-12.9) than in healthy controls. The highest antibody prevalence was found among HPV-16 DNA-positive cervical cancer patients (33%). Our results indicate that in these study groups past infections with the STA considered seems to be of no apparent relevance for cervical carcinogenesis and that the HPV-16 anti-E7 response appears to be associated with cervical cancer.

DNA fingerprinting of Mycobacterium tuberculosis strains from patients with pulmonary tuberculosis in Honduras.

Mycobacterium tuberculosis isolates from 84 patients with pulmonary tuberculosis in Honduras were characterized by restriction fragment length polymorphism analysis. Seventy-three different IS6110 patterns were found; 63 of these were unique and 10 were shared by two to three strains each. Thus, no ongoing spread of any specific clone of bacteria could be demonstrated.

PIP: The relationship among clinical isolates of Mycobacterium tuberculosis from patients with pulmonary tuberculosis in Honduras was investigated through use of DNA fingerprinting. Restriction fragment length polymorphism analysis of isolates from 84 patients revealed 73 different IS6110 patterns. 63 of these patterns were unique and 10 were shared by 2-3 strains each. Smear-positive samples were found for 64 (76%) of all patients, and an isolate derived from at least 1 smear-positive patient was represented in each cluster of strains with identical patterns. Identical or highly related strains--suggestive of ongoing transmission--were more common in men than women, in patients 15-42 years of age, and in those from the Tegucigalpa area. 11 of 76 tested patients were HIV-infected, and only 5 of 11 strains isolated from tuberculosis patients with AIDS had unique IS6110 banding patterns. The fact that no clonal spread of tuberculosis among AIDS patients or those with drug-resistant tuberculosis could be demonstrated indicates that drug-resistant tuberculosis in Honduras emerged in unrelated patients rather than from an ongoing spread of initially resistant M. tuberculosis strains.

Association of infections with human immunodeficiency virus and human papillomavirus in Honduras.

The etiologic role of the oncogenic types of human papillomavirus (HPV) in the development of cervical cancer has been widely proven. Since this cancer occurs more frequently in immunosuppressed individuals, we sought to evaluate the prevalence of HPV infection among human immunodeficiency virus (HIV)-infected and HIV-noninfected prostitutes in Tegucigalpa, Honduras. Cervical scrapes were collected from 23 HIV-seropositive and 28 HIV-seronegative prostitutes for HPV DNA detection by the polymerase chain reaction. Fifty-six percent of the HIV-seropositive women and only 18% of the seronegative women were HPV DNA positive (odds ratio = 6.0). In addition, there was a significant association between seropositivity for HIV with a history of sexually transmitted diseases (P < 0.01). Our data confirm the association between infections with HIV and HPV.

PIP: Numerous studies have revealed a higher prevalence of human papillomavirus (HPV)--etiologically linked to the development of cervical cancer--in women infected with HIV. This study investigated the association of HPV and HIV among 51 prostitutes in Tegucigalpa, Honduras. 23 were HIV-positive. All participants were in their early thirties, had had at least one pregnancy, and experienced their first pregnancy at a mean age of 16 years. Polymerase chain reaction identified HPV DNA in cervical scrapes from 13 (56.5%) HIV-positive women compared with only 5 (18%) HIV-negative prostitutes (odds ratio, 6.0; 95% confidence interval, 1.5-26.7). In addition, there was a significant association between HIV and a history of other sexually transmitted diseases (p 0.01). Since the progression to invasive cervical disease is more aggressive in HIV-infected women, prostitutes and other women at risk of both these infections should receive frequent cytologic screening and counseling.

Anti-insulin-like growth factor-I activity of a novel polysulphonated distamycin A derivative in human lung cancer cell lines.

1. The purpose of this study was to investigate the antiproliferative effect and the modulation of the mitogenic insulin-like growth factor-I (IGF-I) system by FCE 26644 and FCE 27784, two polyanionic sulphonated distamycin A derivative compounds, on two human non-small cell lung cancer (N-SCLC) cell lines. 2. For cell growth studies the colorimetric MTT and the thymidine incorporation assays were performed; the presence of IGF-I and IGF-binding proteins in conditioned media was revealed by radioimmunoassay and Western ligand blot, respectively. Variations at the IGF-I-receptor level were tested by binding studies on cell monolayers. 3. A significant concentration- and time-dependent cytostatic activity of FCE 26644 (IC50 approximately 200 micrograms ml-1 at 72 h) compared to its analogue FCE 27784 (IC50 > 800 micrograms ml-1) was observed in both cell lines studied. The IGF-I-stimulated proliferation of the IGF-I-responsive A549 cell line was abolished by 24 h of FCE 26644 treatment whereas FCE 27784 was inactive. FCE 26644 increased (4 to 6 fold) the secretion of IGF-I-like material and reduced the IGF-I binding (IC50 > 100 micrograms ml-1) in both A549 and Ca-Lu-1 cell lines. FCE 26644 (100 micrograms ml-1) did not affect the KD (approximately 0.5 nM) but reduced the Bmax and the number of receptor sites (50%). 4. Our findings demonstrate that the ability to down-regulate the cell proliferation of N-SCLC cell lines, shown by FCE 26644, depends at least partially, on interference with the "IGF-I mitogenic system'.

Drug-resistant Mycobacterium tuberculosis and atypical mycobacteria isolated from patients with suspected pulmonary tuberculosis in Honduras.

BACKGROUND: Tuberculosis is a major health problem in Central America. In Honduras, with an incidence rate of 81/100,000, it is an increasingly common cause of morbidity and hospitalization. This study was conducted to examine drug-resistant tuberculosis and prevalence of infection with atypical mycobacteria in Honduran patients with suspected pulmonary tuberculosis. METHODS: Pulmonary specimens from 235 Honduran patients with suspected tuberculosis were examined by acid-fast smears and culture. The 95 mycobacterial strains isolated were identified to species level and drug susceptibility tests were carried out. Resistant Mycobacterium tuberculosis strains were tested for susceptibility to six additional drugs. Their possible relationship was studied by DNA restriction fragment length polymorphism. RESULTS: Drug-resistant strains were found in 13 of 85 culture-verified tuberculosis patients, including 10 with isolates of multidrug-resistant bacteria. Seven of the patients with multidrug-resistant tuberculosis had smear-positive disease. Nine of them had a history of specific therapy. Two patients with drug-resistant disease were shown to be infected by identical strains. Only one of 11 HIV-positive patients had drug-resistant tuberculosis. Most resistant strains were susceptible to ciprofloxacin, amikacin, kanamycin, and pyrazinamide. Atypical mycobacteria were isolated from 10 patients with suspected tuberculosis. Seven of them were receiving antituberculosis chemotherapy and five had smear-positive samples. CONCLUSIONS: These results illustrate the importance of mycobacterial culture and subsequent species identification and in vitro susceptibility testing for identification of patients with drug-susceptible or drug-resistant tuberculosis and those infected or colonized with other mycobacteria.