Las características epidemiológicas y clínicas de la epidemia de sífilis en Barcelona / The Epidemiological and Clinical Characteristics of the Epidemic of Syphilis in Barcelona

Introducción: Desde el año 2000 se ha descrito un aumento progresivo de los casos de sífilis en diferentes ciudades europeas, sobre todo en hombres que tienen sexo con hombres (HSH). Las manifestaciones clínicas de la sífilis pueden estar influidas por la coinfección del VIH o por el antecedente de sífilis. El objetivo del presente estudio es describir las características epidemiológicas y clínicas de los casos de sífilis precoz diagnosticados en Barcelona. Métodos: Estudio retrospectivo de casos de sífilis precoz diagnosticados en Barcelona (2003-2013). Se revisaron las historias clínicas y los datos epidemiológicos y clínicos fueron recogidos de forma estructurada. Las variables se compararon según el estatus serológico del VIH y el antecedente de sífilis. Resultados: Se diagnosticaron 1.702 casos de sífilis precoz (37% primaria, 48% secundaria y 14% latente precoz), 93% de ellos en HSH. Entre ellos, el 40% presentaba una coinfección por VIH. Los casos de sífilis en pacientes VIH positivos estaban asociados con un episodio previo de sífilis (aOR, 5,2 [IC del 95%, 3,32-8,24]) y con haber tenido sexo anal desprotegido (aOR, 1,75 [IC del 95%, 1,17-2,63]). Los casos con antecedentes de sífilis se presentaron con menor frecuencia como sífilis primaria (27,5% vs. 40%) (aOR, 0,58 [IC del 95%, 0,44-0,77]). Un año después del tratamiento, la evolución clínica y serológica fue similar en los pacientes VIH positivo y negativo. Conclusiones: La epidemia de sífilis en Barcelona afecta desproporcionalmente a HSH y está estrechamente relacionada con el VIH. La forma de presentación de la sífilis está influida por el antecedente de sífilis y por el VIH, sin diferencias significativas en cuanto a la evolución un año después del tratamiento

Background: Since 2000, substantial increases in syphilis have been reported in metropolitan areas of Western countries, with increases noted among men who have sex with men (MSM). Clinical manifestations of syphilis might be influenced by concomitant VIH infection and previous episodes of syphilis. The objectives of this study were to describe the epidemiological and clinical characteristics of the cases of syphilis diagnosed in Barcelona. Methods: Retrospective study of cases with early syphilis diagnosed in the referral STI Unit of Barcelona from January 2003 to December 2013. Revision of medical records with structured collection of epidemiological and clinical data. Univariate and multivariate statistical analyses comparing the characteristics of MSM cases with and without VIH infection and with and without previous syphilis. Results: A total of 1702 cases of syphilis (37% primary, 48% secondary and 14% early latent) were diagnosed, 93% of them in MSM. Among MSM 40% were coinfected with VIH, VIH-positive cases were associated with a previous syphilis (aOR, 5.2 [95% CI, 3.32-8.24]) and with unprotected anal intercourse (aOR, 1.75 [95%CI, 1.17-2.63]). Cases with a history of syphilis presented less often with primary syphilis compared to those without it (27.5% vs. 40%) (aOR, 0.58 [95% CI, 0.44-0.77]). One year after treatment, the clinical and serological evolution were similar between VIH-positive and VIH-negative cases. Conclusion: The epidemic of syphilis in Barcelona disproportionately affects MSM and is closelly linked to VIH infection. The presentation of syphilis is influenced by VIH infection and by previous history of syphilis, without significant differences in their evolution after one year of treatment

The Epidemiological and Clinical Characteristics of the Epidemic of Syphilis in Barcelona. / Las características epidemiológicas y clínicas de la epidemia de sífilis en Barcelona.

BACKGROUND: Since 2000, substantial increases in syphilis have been reported in metropolitan areas of Western countries, with increases noted among men who have sex with men (MSM). Clinical manifestations of syphilis might be influenced by concomitant VIH infection and previous episodes of syphilis. The objectives of this study were to describe the epidemiological and clinical characteristics of the cases of syphilis diagnosed in Barcelona. METHODS: Retrospective study of cases with early syphilis diagnosed in the referral STI Unit of Barcelona from January 2003 to December 2013. Revision of medical records with structured collection of epidemiological and clinical data. Univariate and multivariate statistical analyses comparing the characteristics of MSM cases with and without VIH infection and with and without previous syphilis. RESULTS: A total of 1702 cases of syphilis (37% primary, 48% secondary and 14% early latent) were diagnosed, 93% of them in MSM. Among MSM 40% were coinfected with VIH, VIH-positive cases were associated with a previous syphilis (aOR, 5.2 [95% CI, 3.32-8.24]) and with unprotected anal intercourse (aOR, 1.75 [95%CI, 1.17-2.63]). Cases with a history of syphilis presented less often with primary syphilis compared to those without it (27.5% vs. 40%) (aOR, 0.58 [95% CI, 0.44-0.77]). One year after treatment, the clinical and serological evolution were similar between VIH-positive and VIH-negative cases. CONCLUSION: The epidemic of syphilis in Barcelona disproportionately affects MSM and is closelly linked to VIH infection. The presentation of syphilis is influenced by VIH infection and by previous history of syphilis, without significant differences in their evolution after one year of treatment.

Increase in gonorrhoea among very young adolescents, Catalonia, Spain, January 2012 to June 2013.

Between January 2012 and June 2013, 27 sexually transmitted infections were reported in adolescents aged 13-15 years in Catalonia, Spain. In the first half of 2013, there were nine cases of gonorrhoea, while in the same period of 2012, there was one. In June 2013, two gonorrhoea cases aged 13-14 years, linked to a common source through a social network, were reported. The public health response should be adapted to this vulnerable population.

Lymphogranuloma venereum: a hidden emerging problem, Barcelona, 2011.

From the beginning of 2007 until the end of 2011, 146 cases of lymphogranuloma venereum (LGV) were notified to the Barcelona Public Health Agency. Some 49% of them were diagnosed and reported in 2011, mainly in men who have sex with men. Almost half of them, 32 cases, were reported between July and September. This cluster represents the largest since 2004. This article presents the ongoing outbreak of LGV in Barcelona.

[HIV infection and other sexually-transmitted infections among immigrants in Barcelona]. / Infección por el virus de la inmunodeficiencia humana y otras infecciones de transmisión sexual en inmigrantes de Barcelona*

BACKGROUND: Immigration is a recent phenomenon in Spain. Certain subgroups of the immigrant population may be vulnerable to acquiring sexually transmitted infections (STI). MATERIAL AND METHODS: Descriptive study of the seroprevalenceof certain STI (HIV, hepatitis B and syphilis) and the general characteristicsn of persons tested for HIV infection in a specialized clinic in Barcelona during the year 2000. RESULTS: Seroprevalence of HIV was similar in immigrants and native residents(1.8% vs. 1.7% respectively). However, the seroprevalences of hepatitis B virus (anti-HBc) (19.5% vs. 8.3%) and syphilis (RPR 1 TPHA) (3.2% vs. 1.1%), as well as other STI and the practice of prostitution, were higher in immigrants. CONCLUSIONS: Several STI, including hepatitis B and syphilis, were found more frequently in immigrants than in the native population, whereas HIV seroprevalence was similar in the two groups.

Absence of Fas (CD95) and FasL (CD95L) immunohistochemical expression suggests Fas/FasL-mediated apoptotic signal is not relevant in cutaneous Kaposi's sarcoma lesions.

It has been suggested that Fas ligand (FasL), expressed by several neoplastic cell lines and some tumors in vivo, is able to trigger the apoptotic process in activated T-lymphocytes and may constitute a key element of the immunological escape mechanisms used by many types of neoplasia. In order to evaluate the possible role of Fas-mediated apoptosis in Kaposi's sarcoma (KS), we have studied the immunocytochemical expression of Fas and FasL in biopsy specimens showing different histopathological stages of classic KS (C-KS) and AIDS-associated KS (AIDS-KS), as well as in cultured cells derived from C-KS lesions. KS biopsy tissue failed to show Fas expression in all epidemiologic forms and histopathologic stages studied, while FasL positivity was present in a small number of cells in just a few cases. Double immunostaining ruled out the lymphocytic nature of these cells, whose morphology in adjacent sections stained with hematoxylin and eosin was consistent with KS cells. In contrast, cultured KS cells exhibited strong immunocytochemical cytoplasmic expression of both Fas and FasL. These findings indicate that the Fas-FasL system does not play a major role as a trigger of apoptosis in KS cells in vivo and that the upregulation of these molecules observed in KS cells in vitro probably is the result of cell stress induced by growth in culture.

Endotoxin contamination may be responsible for the unexplained failure of human pancreatic islet transplantation.

Clinical transplantation of human islets has a disappointingly low rate of success. We report here the identification of a possible causative factor: endotoxin present in the collagenase preparations used to disperse the pancreatic tissue before islet purification and transplantation. Supporting evidence includes (1) detection of unexpectedly high levels of endotoxin in most collagenase solutions currently used to digest human pancreases; (2) demonstration that supernatants generated during islet separation are able to induce the inflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha (TNF-alpha) in macrophages; and (3) induction of IL-1, IL-6, and TNF-alpha in the islets during the separation procedure. Cytokine expression was assessed by reverse transcription-polymerase chain reaction and, for TNF-alpha, confirmed by enzyme-linked immunoabsorbent assay. It is proposed that endotoxin and locally induced cytokines carried over with the graft activate the endothelium and promote lymphomonocytic infiltration of grafted islets and surrounding liver tissue favoring primary nonfunction and early rejection. These results also have implications for the numerous experimental procedures that use collagenase, and they point to possible ways to improve islet preparation and transplantation protocols.

Hyperexpression of transporter in antigen processing-1 (TAP-1) in thyroid glands affected by autoimmunity: a contributing factor to the breach of tolerance to thyroid antigens?

According to the 'aberrant HLA expression' hypothesis, endocrine autoimmunity is driven by presentation of self antigens by target cells over-expressing HLA molecules. In autoimmune thyroid diseases (AITD), thyroid follicular cells (thyrocytes) over-express HLA class I and HLA class II molecules. Since efficient presentation of endogenous peptides via class I requires transporters that translocate endogenous peptides from the cytoplasm to the endoplasmic reticulum, i.e. transporters associated with antigen processing (TAP) -1 and -2, the capability of thyrocytes to express TAP and whether TAP is hyperexpressed in AITD glands are issues relevant to the above hypothesis. Results from immunofluorescence and Northern blotting studies on primary thyrocyte cultures and on a thyroid cell line demonstrate that thyrocytes express constitutively TAP-1 at a low level, and that this expression is readily induced by interferon-gamma (IFN-gamma) and to a lesser extent by IFN-alpha. In AITD, but not in non-autoimmune glands, thyrocytes hyperexpress TAP-1, as demonstrated by both immunohistopathology and flow cytometry. The cytokine pattern does not bear, as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR), a clear relationship with TAP-1 expression. These results have broad implications and suggest that the core concept of the 'aberrant HLA expression' hypothesis of endocrine autoimmunity could be incorporated in the currently prevailing view of 'autoimmunity by breach of peripheral tolerance'.

Advantages of using a cell separator and metrizamide gradients for human islet purification.

Human islet transplantation has a high rate of failure, often due to primary nonfunction, which suggests that islets are damaged during the processing of the pancreas. The preparation of human islets for transplantation is still a complex process that requires large teams of surgical and laboratory personnel. To overcome this problem, we have adopted the use of the IBM 2991 COBE cell separator and a metrizamide/Ficoll density medium that is easy to prepare. Twenty-seven pancreatic glands have been processed using the COBE cell separator, 23 of which were purified in metrizamide/Ficoll gradients and 4 in bovine serum albumin gradients. The results show an improvement of recovery and viability in these preparations when compared retrospectively with manual gradients. More importantly, the time required for purification was shortened to one fourth the usual time and total processing time is about half as long. Moreover, a team of two laboratory staff was regularly able to prepare islets for transplantation, reducing the separation time from 7 hr to 3.5 hr. We conclude that the automatic cell separator and metrizamide-based separation medium are useful modifications of current islet purification methods.

K-ras gene point mutation: a stable tumor marker in non-small cell lung carcinoma.

K-ras gene point mutation is a highly frequent event in human malignancy. About one third of non-small cell lung cancer (NSCLC) patients harbor K-ras gene point mutational activations. This study investigates the prevalence of K-ras mutation in autopsy tumors with NSCLC, and the correlation of K-ras gene point mutations between primary tumors and metastases in NSCLC. Formalin-fixed, paraffin-embedded tissue sections of 15 primary lung tumors and their metastases, (obtained from autopsy), were examined for the presence of point mutations in K-ras gene codon 12, 13 and 61 by oligodeoxynucleotide hybridization analysis of DNA fragments, amplified by polymerase chain reaction (PCR). K-ras gene point mutations were detected in five cases of lung carcinoma, of which four were adenocarcinomas and one was squamous cell carcinoma. In each of these cases, identical K-ras gene mutations were found in the DNA of both the primary tumor and its corresponding distant metastases. Activating K-ras base-substitutions correlate well between the primary tumor and its corresponding metastases in NSCLC. In the negative cases where no K-ras mutation was found in the primary tumors, no newly acquired K-ras mutation appeared in the metastases. Our study indicates that K-ras point mutation serves as a stable tumor marker in NSCLC.

Prognostic impact of mutated K-ras gene in surgically resected non-small cell lung cancer patients.

Mutated K-ras oncogenes have been detected in a third of lung adenocarcinomas, located usually in codon 12, its presence correlating negatively with survival. To further define the role of K-ras point mutations in non-small cell lung cancer, we studied the presence of mutated K-ras genes in surgical specimens from 66 patients. Polymerase chain reaction was performed from sections of formalin-fixed paraffin-embedded tissue. We screened for point mutations in codons 12, 13 and 61 of the K-ras gene by dot blot hybridization analysis with mutation-specific oligonucleotide probes. Ras gene mutations were present in 13 of 66 carcinomas (20%), nine in codon 12 and four in codon 61. Three squamous cell carcinomas harbored two different point mutations in K-ras codon 12. Mutated K-ras genes were found more frequently in squamous cell carcinomas (eight of 38) than in adenocarcinoma (three of 22). Analysis of nucleotide sequence disclosed a multifarious mutation pattern of K-ras codon 12, where the most common conversion was from glycine (GGT) to valine (GTT). K-ras point mutation positive subset had poorer survival, nine of the 13 patients died during the follow-up period as compared with 22 of 53 patients with no mutation in the K-ras gene (P = 0.01). The difference was also strikingly significant when stratified according to node status.

Expression of glutamic acid decarboxylase (GAD) in the alpha, beta and delta cells of normal and diabetic pancreas: implications for the pathogenesis of type I diabetes.

One of the paradoxes of insulin-dependent diabetes mellitus is that the destruction of the pancreatic islets' endocrine cells is restricted to the insulin-producing beta cells, whereas the main autoantibodies, islet cell antibodies (ICA), are directed against all endocrine islet cells. GAD has recently been proposed as the main target of the humoral and cellular autoimmune attack to the islets, and since in rat pancreas this enzyme was expressed only in the beta cells, this provided an explanation for the cell specificity of the destructive process. The finding of GAD-positive cells in the islets of two diabetic patients, one of whom had completely lost the beta cells, led us to study in detail the distribution of GAD in normal human islet cells using a panel of GAD antisera and the double indirect immunofluorescence technique on cryostat sections, monolayer cultures and cytosmears. The results showed that GAD is present not only in the cytoplasm of beta cells but also in 69% of the alpha and 27% of the delta cells. GAD was not present, however, on the surface of the islet cells. These results suggest that the cellular distribution of GAD can not by itself explain the selectivity of beta cell destruction in insulin-dependent diabetes mellitus.

Non-association between 9.2 KB PvuII RFLP and seronegative spondyloarthropathies in Spain.

Several studies of DNA restriction fragment length polymorphism (RFLP) in ankylosing spondylitis (AS) have been carried out. The association between a recently identified class I HLA 9.2 kb PvuII RFLP and AS remain controversial. In order to evaluate this possible association in an Euro-Caucasian population, the genomic DNA of 42 AS patients and 18 patients with Reiter's syndrome (RS) and 42 healthy controls was analysed. Non-association between 9.2 kb PvuII RFLP and AS or RS was observed. As described previously, a strong association between this fragment and HLA-A3 and/or HLA-A9 antigens was demonstrated. A study of two families showed that this RFLP segregates with HLA-A3 and/or HLA-A9 and independently of the HLA-B27. Our findings support the view that the 9.2 kb PvuII fragment is not universally associated with AS.