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1.
Artigo em Inglês | MEDLINE | ID: mdl-38822578

RESUMO

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38822598

RESUMO

INTRODUCTION: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early. OBJECTIVES: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects. MATERIALS AND METHODS: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives. RESULTS: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases. CONCLUSIONS: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term.

3.
Br J Surg ; 108(11): 1388-1395, 2021 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-34508549

RESUMO

BACKGROUND: A permanent stoma after anterior resection for rectal cancer is common. Preoperative counselling could be improved by providing individualized accurate prediction modelling. METHODS: Patients who underwent anterior resection between 2007 and 2015 were identified from the Swedish Colorectal Cancer Registry. National Patient Registry data were added to determine presence of a stoma 2 years after surgery. A training set based on the years 2007-2013 was employed in an ensemble of prediction models. Judged by the area under the receiving operating characteristic curve (AUROC), data from the years 2014-2015 were used to evaluate the predictive ability of all models. The best performing model was subsequently implemented in typical clinical scenarios and in an online calculator to predict the permanent stoma risk. RESULTS: Patients in the training set (n = 3512) and the test set (n = 1136) had similar permanent stoma rates (13.6 and 15.2 per cent). The logistic regression model with a forward/backward procedure was the most parsimonious among several similarly performing models (AUROC 0.67, 95 per cent c.i. 0.63 to 0.72). Key predictors included co-morbidity, local tumour category, presence of metastasis, neoadjuvant therapy, defunctioning stoma use, tumour height, and hospital volume; the interaction between age and metastasis was also predictive. CONCLUSION: Using routinely available preoperative data, the stoma outcome at 2 years after anterior resection for rectal cancer can be predicted fairly accurately.


Usually, the goal of rectal cancer surgery is to remove the tumour and construct a bowel join. Sometimes, it is necessary to construct a stoma, which may become permanent. Swedish registry data were used to develop and test a statistical model to forecast the risk of a stoma 2 years after surgery. In addition, an online calculator was developed. The model performed reasonably well, and can be used to inform the patient and surgeon before surgery of the risk of a permanent stoma.


Assuntos
Colectomia/métodos , Neoplasias Retais/cirurgia , Sistema de Registros , Estomas Cirúrgicos/normas , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Suécia
4.
Clin Genet ; 89(3): 359-66, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25959749

RESUMO

RASopathies are a clinically heterogeneous group of conditions caused by mutations in 1 of 16 proteins in the RAS-mitogen activated protein kinase (RAS-MAPK) pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins; however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma.


Assuntos
Sistema de Sinalização das MAP Quinases , Mutação de Sentido Incorreto , Síndrome de Noonan/metabolismo , Proteínas ras/genética , Adolescente , Animais , Animais Geneticamente Modificados , Criança , Pré-Escolar , Modelos Animais de Doenças , Anormalidades do Olho/genética , Feminino , Humanos , Lactente , Recém-Nascido , Extremidade Inferior , Linfedema/genética , Masculino , Síndrome de Noonan/genética , Conformação Proteica , Peixe-Zebra/genética , Proteínas ras/metabolismo
5.
J Viral Hepat ; 18(2): 106-18, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20158602

RESUMO

The spread of hepatitis C virus (HCV) in Sweden in the 1970s indicated that serious liver complications (SLC) would increase in the 2000s. The aim of this study was to analyse the burden of HCV-associated inpatient care in Sweden, to demonstrate the changes over time and to compare the findings with a noninfected population. The HCV-cohort (n: 43,000) was identified from the national surveillance database 1990-2006, and then linked to national registers to produce an age-, sex-, and region-matched noninfected comparison population (n: 215,000) and to obtain information on demographics, cancers, inpatient care and prescriptions. Cox regression was used to estimate the likelihood (hazard ratios) for admission to hospital in the HCV compared with the noninfected cohort. The hazard ratios were 4.03 (95% CI: 3.98-4.08) for all care, 77.52 (71.02-84.60) for liver-related care and 40.74 (30.58-54.27) for liver cancer care. The admission rate in the HCV-cohort compared with the noninfected cohort, the rate ratio (age- and sex-adjusted) for all inpatient care was 5.91 (95% CI: 5.87-5.94), and the rate ratio for liver-related care was 70.05 (66.06-74.28). In the HCV-cohort, 45% of all episodes were for psychiatric, mostly drug-related, care. Inpatient care for SLC increased in the 2000s. To conclude, drug-related care was common in the HCV-infected cohort, the demand for liver-related care was very high, and SLC increased notably in the 2000s, indicating that the burden of inpatient care from serious liver disease in HCV-infected individuals in Sweden is an increasing problem.


Assuntos
Hepatite C/epidemiologia , Hospitalização/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Hepatite C/patologia , Hospitalização/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Suécia/epidemiologia , Adulto Jovem
6.
Int J Microbiol ; 20112011.
Artigo em Inglês | MEDLINE | ID: mdl-20885922

RESUMO

Tularemia, caused by the bacterium Francisella tularensis, where F. tularensis subspecies holarctica has long been the cause of endemic disease in parts of northern Sweden. Despite this, our understanding of the natural life-cycle of the organism is still limited. During three years, we collected surface water samples (n = 341) and sediment samples (n = 245) in two areas in Sweden with endemic tularemia. Real-time PCR screening demonstrated the presence of F. tularenis lpnA sequences in 108 (32%) and 48 (20%) of the samples, respectively. The 16S rRNA sequences from those samples all grouped to the species F. tularensis. Analysis of the FtM19InDel region of lpnA-positive samples from selected sampling points confirmed the presence of F. tularensis subspecies holarctica-specific sequences. These sequences were detected in water sampled during both outbreak and nonoutbreak years. Our results indicate that diverse F. tularensis-like organisms, including F. tularensis subsp. holarctica, persist in natural waters and sediments in the investigated areas with endemic tularemia.

7.
Euro Surveill ; 13(21)2008 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-18761966

RESUMO

In Sweden, infection with hepatitis C virus (HCV) has been a notifiable disease since 1990, when diagnostic methods became available. Blood donor screening indicated that about 0.5% of the Swedish population (9 millions) had been HCV infected. Here we present the Swedish hepatitis C epidemic based on data from all the HCV notifications 1990-2006. During this time about 42,000 individuals (70% men) were diagnosed and reported as HCV infected. The majority (80%) were born in 1950 or later, with a high percentage (60%) born in the 1950s and 1960s. Younger people, 15-24 years old at notification, were reported on the same level each year. The main reported routes of HCV transmission were intravenous drug use in 65%, blood transfusions/products in 6%, and sexual in 2%, though unknown or not stated in 26%. Approximately 6,000 of all notified individuals have died during the study period. To conclude, the Swedish HCV epidemic is highly related to the increase of intravenous drug use in the late 1960s and 1970s, with a high proportion of people now chronically infected for more than 25 years, resulting in an increase of severe liver complications in form of cirrhosis and hepatocellular carcinoma. Furthermore the unchanged number of notifications of newly infected younger people indicates an ongoing HCV epidemic.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Hepatite C/epidemiologia , Vigilância da População , Medição de Risco/métodos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Adolescente , Adulto , Idoso , Comorbidade , Humanos , Incidência , Pessoa de Meia-Idade , Fatores de Risco , Suécia/epidemiologia
8.
Klin Monbl Augenheilkd ; 224(9): 727-32, 2007 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-17846963

RESUMO

PURPOSE: Ranibizumab (Lucentis) stabilizes or improves visual acuity in a high percentage of patients with age-related macular degeneration (AMD). As this therapy is associated with significant costs, the aim of this study was to provide a cost-utility analysis, which considers both costs and utility of a therapy with ranibizumab in an economic model. METHODS: The incremental utility for the patient was modelled based on visual acuity data of the MARINA and ANCHOR study. The utility data used assume that the better seeing eye is affected. The study groups used for comparison consisted of patients who only received best supportive care, e. g., low-vision aids. The baseline scenario of the model assumes 6 treatments per year over a 2 year time period - based on the assessment of an expert panel. Treatment costs were based on German pharmacy prices and recommendations for reimbursement of the intravitreal injections. In a univariate sensitivity analysis all important parameters were varied to assess the stability of the results. RESULTS: The baseline scenario yields for predominantly classic lesions 16,882 euro/QALY (quality adjusted life year), for minimally classic CNV 24,766 euro/QALY and for occult CNV 26,170 euro/QALY. If a distribution of the CNV types with 18 - 25 - 57 % is assumed, the mean cost of therapy with ranibizumab amounts to 24,147 euro/QALY. Sensitivity analysis showed that all reasonable variations yielded results which are considered cost-effective ( 0.4) visual acuity, for a variation of costs per treatment of +/- 20 %, and a prolonged treatment duration of 3 years. CONCLUSIONS: In the investigated szenario a therapy of neovascular AMD with ranibizumab is cost-effective for all angiographic subtypes as well as in the sensitivity analysis.


Assuntos
Anticorpos Monoclonais/economia , Custos de Medicamentos/estatística & dados numéricos , Degeneração Macular/economia , Anos de Vida Ajustados por Qualidade de Vida , Neovascularização Retiniana/economia , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Análise Custo-Benefício , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Alemanha , Humanos , Injeções , Degeneração Macular/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab , Neovascularização Retiniana/tratamento farmacológico , Acuidade Visual/efeitos dos fármacos , Corpo Vítreo
9.
Antimicrob Agents Chemother ; 50(9): 3028-32, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16940098

RESUMO

Samples from patients with Clostridium difficile-associated diarrhea (CDAD) that were randomized to fusidic acid (n = 59) or metronidazole (n = 55) therapy for 7 days were cultured for Clostridium difficile in feces on days 1, 8 to 13, and 35 to 40. Of the patients who were culture positive only before treatment, 77% (36/47) were permanently cured (no treatment failure and no clinical recurrence), compared to 54% (22/41) of those with persistence of C. difficile at one or both follow-ups (P = 0.03). A similar association between bacterial persistence and a worse outcome of therapy was seen in both treatment groups. Resistance to fusidic acid was found in 1 of 88 pretherapy isolates available, plus in at least 1 subsequent isolate from 55% (11/20) of patients who remained culture-positive after fusidic acid therapy. In 10 of these 11 patients, the resistant follow-up isolate(s) belonged to the same PCR ribotype as the susceptible day 1 isolate, confirming frequent emergence of resistance to fusidic acid during treatment. Despite this, 5 of these 11 patients were permanently cured with fusidic acid, relative to 5 of 9 patients with susceptible C. difficile at follow-up (P = 1.0). None of the 36 PCR ribotypes of C. difficile identified was associated with any particular clinical outcome or emergence of fusidic acid resistance. In conclusion, culture positivity for C. difficile was common after both fusidic acid and metronidazole therapy and was associated with treatment failure or recurrence of CDAD. Development of resistance in C. difficile was frequent in patients given fusidic acid, but it was without apparent negative impact on therapeutic efficacy in the actual CDAD episode.


Assuntos
Clostridioides difficile/efeitos dos fármacos , Diarreia/tratamento farmacológico , Diarreia/microbiologia , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/microbiologia , Ácido Fusídico/uso terapêutico , Antibacterianos/uso terapêutico , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Método Duplo-Cego , Farmacorresistência Bacteriana , Humanos , Metronidazol/uso terapêutico , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase/métodos , Estudos Prospectivos , Resultado do Tratamento
10.
Genes Immun ; 7(6): 503-13, 2006 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16826236

RESUMO

Tularemia is a febrile disease caused by the highly contagious bacterium Francisella tularensis. We undertook an analysis of the transcriptional response in peripheral blood during the course of ulceroglandular tularemia by use of Affymetrix microarrays comprising 14,500 genes. Samples were obtained from seven individuals at five occasions during 2 weeks after the first hospital visit and convalescent samples 3 months later. In total, 265 genes were differentially expressed, 95 of which at more than one time point. The differential expression was verified with real-time quantitative polymerase chain reaction for 36 genes (R(2)=0.590). The most prominent changes were noted in samples drawn on days 2-3 and a considerable proportion of the upregulated genes appeared to represent an interferon-gamma-induced response and also a proapoptotic response. Genes involved in the generation of innate and acquired immune responses were found to be downregulated, presumably a pathogen-induced event. A logistic regression analysis revealed that seven genes were good predictors of the early phase of tularemia. This is the first description of the transcriptional host response to ulceroglandular tularemia and the study has identified gene subsets relevant to the pathogenesis of the disease and subsets that may serve as early diagnostic biomarkers.


Assuntos
Perfilação da Expressão Gênica , Tularemia/sangue , Tularemia/genética , Idoso , Surtos de Doenças , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Análise de Regressão , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Suécia/epidemiologia , Regulação para Cima
11.
J Clin Microbiol ; 42(8): 3635-43, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15297509

RESUMO

All episodes of Clostridium difficile associated diarrhea (CDAD) diagnosed in a defined population of 274,000 including one tertiary and two primary hospitals and their catchment areas were studied during 12 months. The annual CDAD incidence in the county was 97 primary episodes per 100,000, and 78% of all episodes were classified as hospital associated with a mean incidence of 5.3 (range, 1.4 to 6.5) primary episodes per 1,000 admissions. The incidence among hospitalized individuals was 1,300-fold higher than that in the community (33,700 versus 25 primary episodes per 100,000 persons per year), reflecting a 37-fold difference in antibiotic consumption (477 versus 13 defined daily doses [DDD]/1,000 persons/day) and other risk factors. Three tertiary hospital wards with the highest incidence (13 to 36 per 1,000) had CDAD patients of high age (median age of 80 years versus 70 years for other wards, P < 0.001), long hospital stay (up to 25 days versus 4 days), or a high antibiotic consumption rate (up to 2,427 versus 421 DDD/1,000 bed days). PCR ribotyping of C. difficile isolates available from 330 of 372 CDAD episodes indicated nosocomial acquisition of the strain in 17 to 27% of hospital-associated cases, depending on the time interval between index and secondary cases allowed (2 months or up to 12 months), and only 10% of recurrences were due to a new strain of C. difficile (apparent reinfection). In other words, most primary and recurring episodes were apparently caused by the patient's endogenous strain rather than by one of hospital origin. Typing also indicated that a majority of C. difficile strains belonged to international serotypes, and the distribution of types was similar within and outside hospitals and in primary and relapsing CDAD. However, type SE17 was an exception, comprising 22% of hospital isolates compared to 6% of community isolates (P = 0.008) and causing many minor clusters and a silent nosocomial outbreak including 36 to 44% of the CDAD episodes in the three high-incidence wards.


Assuntos
Clostridioides difficile , Infecção Hospitalar/microbiologia , Enterocolite Pseudomembranosa/epidemiologia , Clostridioides difficile/classificação , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Diarreia/epidemiologia , Diarreia/microbiologia , Fezes/microbiologia , Humanos , Pacientes Internados/estatística & dados numéricos , Epidemiologia Molecular/métodos , Recidiva , Suécia/epidemiologia
13.
J Infect Dis ; 186 Suppl 1: S66-70, 2002 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-12353189

RESUMO

The objective of this multicenter, randomized, double-blind, noninferiority trial was to investigate valacyclovir as treatment for facial herpes simplex virus (HSV) outbreaks. In total, 308 otherwise healthy outpatients self-initiated therapy with valacyclovir, either 1000 mg twice daily for 1 day or 500 mg twice daily for 3 days, for treatment of one facial HSV episode. Aborted lesions were the primary end point. Secondary end points included episode and pain resolution and lesion healing. By regimen (1 or 3 days), aborted lesions occurred in 42.2% versus 46.7% of patients, treatment difference, -4.5% (95% confidence interval, -16.3% to 7.4%; P=.49). Subgroup findings showed that about half the episodes aborted when therapy started during the prodrome/macule stages or within 6 h of first symptoms. Episode and pain resolved rapidly, with results similar for both treatments. Adverse events were infrequent and similar for the two regimens.


Assuntos
Aciclovir/análogos & derivados , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Dermatoses Faciais/tratamento farmacológico , Herpes Simples/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Valina/análogos & derivados , Valina/uso terapêutico , Aciclovir/administração & dosagem , Administração Oral , Adolescente , Adulto , Idoso , Dinamarca , Método Duplo-Cego , Esquema de Medicação , Dermatoses Faciais/patologia , Feminino , Finlândia , Herpes Simples/patologia , Humanos , Lituânia , Masculino , Pessoa de Meia-Idade , Noruega , Fatores de Tempo , Resultado do Tratamento , Valaciclovir , Valina/administração & dosagem
14.
Clin Genet ; 60(1): 77-82, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11531975

RESUMO

We report on a newborn female patient with a de novo pure partial duplication of 7q. The clinical features are compared with those of 19 cases from the literature with pure partial duplication of different segments of 7q. Conventional cytogenetic investigation led to the diagnosis of duplication of bands q21.3 to q35. This was confirmed by chromosome painting and by fluorescence in situ hybridization with different YAC probes from the duplicated region.


Assuntos
Aberrações Cromossômicas , Cromossomos Humanos Par 7/genética , Pré-Escolar , Bandeamento Cromossômico , Análise Citogenética , Evolução Fatal , Feminino , Duplicação Gênica , Humanos , Hibridização in Situ Fluorescente , Lactente
15.
Sex Transm Dis ; 28(5): 252-8, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11354262

RESUMO

BACKGROUND: Chlamydia trachomatis has been recognized as a major sexually transmitted infection in North America and Western Europe during the past two decades. The incidence of C trachomatis in Finland has been continuously high throughout the 1990s. OBJECTIVES: As the epidemic of C trachomatis infection continues in Finland, there is a need to obtain up-to-date information on the prevalence and patient profiles in the planning of preventive strategies. METHODS: A nationwide sentinel clinic network consisting of seven sexually transmitted disease (STD) and five general student health clinics was established in 1995. Data were collected during a 3-year period (1995-1997) from 3,686 patients with and 32,230 patients without C trachomatis using a self-administered questionnaire. RESULTS: The prevalence of chlamydia was 8.4% in the STD clinics and 5.3% in the general clinics; 90% of the infections were endemic. The prevalence was highest in the youngest age group (15-19 years; 16% in females, 14% in males). The patients with chlamydia were significantly younger (mean age: men 26.6 years, women 23.7 years) than those without chlamydia. Women with chlamydia used oral contraceptives or intrauterine devices (IUD) significantly more often (59%) than women without chlamydia (42%). A high number of sex partners and a history of previous chlamydia during the preceding 12 months were also risk factors. Men contracted chlamydia frequently from a casual partner (61%) but rarely from a commercial sex worker (2%). For women, the source partner was most often a regular one (61%). The median time from exposure to attendance was 34 days, and was highest when the source partner was a spouse. One third of the patients could have spread chlamydia to a new partner before the diagnosis. CONCLUSIONS: C trachomatis infection is spread all over Finland, and the risk factors include younger age, high number of sex partners, and use of oral contraceptives or IUDs. Source partner analysis focused attention on the importance of transmission from regular partners, especially in women. The time from transmission to diagnosis was long, and any effort to shorten this period would be an effective preventive strategy.


Assuntos
Infecções por Chlamydia/epidemiologia , Chlamydia trachomatis , Vigilância de Evento Sentinela , Parceiros Sexuais , Adolescente , Adulto , Fatores Etários , Infecções por Chlamydia/diagnóstico , Infecções por Chlamydia/prevenção & controle , Infecções por Chlamydia/transmissão , Chlamydia trachomatis/isolamento & purificação , Anticoncepcionais Orais/efeitos adversos , Feminino , Finlândia/epidemiologia , Humanos , Incidência , Dispositivos Intrauterinos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Inquéritos e Questionários , Fatores de Tempo
16.
Hum Mol Genet ; 10(3): 201-10, 2001 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-11159938

RESUMO

Balanced translocations affecting the paternal copy of 15q11--q13 are a rare cause of Prader-Willi syndrome (PWS) or PWS-like features. Here we report on the cytogenetic and molecular characterization of a de novo balanced reciprocal translocation t(X;15)(q28;q12) in a female patient with atypical PWS. The translocation breakpoints in this patient and two previously reported patients map 70-80 kb distal to the SNURF-SNRPN gene and define a breakpoint cluster region. The breakpoints disrupt one of several hitherto unknown 3' exons of this gene. Using RT--PCR we demonstrate that sequences distal to the breakpoint, including the recently identified C/D box small nucleolar RNA (snoRNA) gene cluster HBII-85 as well as IPW and PAR1, are not expressed in the patient. Our data suggest that lack of expression of these sequences contributes to the PWS phenotype.


Assuntos
Autoantígenos/genética , Cromossomos Humanos Par 15/genética , Proteínas Nucleares , Proteínas/genética , Ribonucleoproteínas Nucleares Pequenas , Translocação Genética , Adulto , Processamento Alternativo , Sequência de Bases , Bandeamento Cromossômico , Quebra Cromossômica/genética , Análise Citogenética , DNA/genética , DNA/metabolismo , Metilação de DNA , DNA Complementar/química , DNA Complementar/genética , Éxons/genética , Feminino , Expressão Gênica , Humanos , Hibridização in Situ Fluorescente , Masculino , Dados de Sequência Molecular , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/patologia , Análise de Sequência de DNA , Transcrição Gênica , Cromossomo X/genética , Proteínas Centrais de snRNP
18.
Am J Hum Genet ; 65(1): 111-24, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10364523

RESUMO

Campomelic dysplasia (CD), a skeletal malformation syndrome with or without XY sex reversal, is usually caused by mutations within the SOX9 gene on distal 17q. Several CD translocation and inversion cases have been described with breakpoints outside the coding region, mapping to locations >130 kb proximal to SOX9. Such cases are generally less severely affected than cases with SOX9 coding-region mutations, as is borne out by three new translocation cases that we present. We have cloned the region extending 1.2 Mb upstream of the SOX9 gene in overlapping bacterial-artificial-chromosome and P1-artificial-chromosome clones and have established a restriction map with rare-cutter enzymes. With sequence-tagged-site-content mapping in somatic-cell hybrids, as well as with FISH, we have precisely mapped the breakpoints of the three new and of three previously described CD cases. The six CD breakpoints map to an interval that is 140-950 kb proximal to the SOX9 gene. With exon trapping, we could isolate five potential exons from the YAC 946E12 that spans the region, four of which could be placed in the contig in the vicinity of the breakpoints. They show the same transcriptional orientation, but only two have an open reading frame (ORF). We failed to detect expression of these fragments in several human and mouse cDNA libraries, as well as on northern blots. Genomic sequence totaling 1,063 kb from the SOX9 5'-flanking region was determined and was analyzed by the gene-prediction program GENSCAN and by a search of dbEST and other databases. No genes or transcripts could be identified. Together, these data suggest that the chromosomal rearrangements most likely remove one or more cis-regulatory elements from an extended SOX9 control region.


Assuntos
Osso e Ossos/anormalidades , Proteínas de Grupo de Alta Mobilidade/genética , Fatores de Transcrição/genética , Translocação Genética , Adolescente , Animais , Sequência de Bases , Criança , Cromossomos Humanos Par 17 , Mapeamento de Sequências Contíguas , Éxons , Feminino , Biblioteca Gênica , Genes Dominantes , Humanos , Hibridização in Situ Fluorescente , Masculino , Camundongos , Repetições de Microssatélites , Modelos Genéticos , Dados de Sequência Molecular , Fatores de Transcrição SOX9 , Sitios de Sequências Rotuladas , Síndrome
19.
Eur J Hum Genet ; 6(3): 213-25, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9781025

RESUMO

DiGeorge syndrome (DGS) is a developmental field defect, characterised by absent/hypoplastic thymus and parathyroid, and conotruncal heart defects, with haploinsufficiency loci at 22q (DGS1) and 10p (DGS2). We performed fluorescence in situ hybridisations (FISH) and polymerase chain reaction (PCR) analyses in 12 patients with 10p deletions, nine of them with features of DGS, and in a familial translocation 10p;14q associated with midline defects. The critical DGS2 region is defined by two DGS patients, and maps within a 1 cM interval including D10S547 and D10S585. The other seven DGS patients are hemizygous for both loci. The breakpoint of the reciprocal translocation 10p;14q maps at a distance of at least 12 cM distal to the critical DGS2 region. Interstitial and terminal deletions described are in the range of 10-50 cM and enable the tentative mapping of loci for ptosis and hearing loss, features which are not part of the DGS clinical spectrum.


Assuntos
Cromossomos Humanos Par 10 , Síndrome de DiGeorge/genética , Deleção de Sequência , Linhagem Celular Transformada , Mapeamento Cromossômico , Feminino , Humanos , Hibridização In Situ , Lactente , Recém-Nascido , Masculino , Reação em Cadeia da Polimerase , Translocação Genética
20.
J Clin Microbiol ; 36(6): 1489-93, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9620366

RESUMO

The diagnostic performance of a PCR test (Roche Cobas Amplicor CT/NG Test) and that of a ligase chain reaction (LCR) test (Abbott LCx Chlamydia trachomatis assay) were compared by using endocervical and urethral swab specimen culture as a reference test. First-void urine (FVU) and endocervical and urethral swab specimens were collected from 1,015 unselected patients attending a sexually transmitted disease clinic and a clinic for adolescents in Helsinki, Finland. Chlamydia trachomatis was cultured from samples from the endocervix or urethra. PCR was performed with fresh and frozen urine and the culture transport medium. LCR was performed with fresh and frozen urine and LCx swab transport medium. Diagnostic consistency and diagnostic accuracy were statistically tested. The test results were identical for 984 patients (97%). Discrepant results were observed for 31 patients. Overall, LCR and PCR showed excellent kappa coefficients of consistency for both swab and FVU specimens (0.93 and 0.95, respectively). Sixty-one patients (6%) were culture positive. Testing of FVU by LCR or PCR increased the overall positivity rates to 7.0 and 7.7%, respectively. While PCR of FVU detected the greatest number of C. trachomatis infections (sensitivity, 96.1%), for some PCR-positive FVU specimens the results could not be confirmed (specificity, 99.6%). PCR and LCR were more sensitive than culture (sensitivities, 92 and 93% versus 79% for culture) in the diagnosis of genital C. trachomatis infection. In conclusion, both tests can be recommended for use in the clinical laboratory and for the screening of asymptomatic C. trachomatis infections.


Assuntos
Infecções por Chlamydia/diagnóstico , Chlamydia trachomatis/isolamento & purificação , Doenças Urogenitais Femininas/diagnóstico , Doenças Urogenitais Masculinas , Técnicas de Amplificação de Ácido Nucleico , Reação em Cadeia da Polimerase/métodos , Colo do Útero/microbiologia , Infecções por Chlamydia/urina , DNA Ligases/metabolismo , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Doenças Urogenitais Femininas/urina , Congelamento , Humanos , Masculino , Valor Preditivo dos Testes , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Uretra/microbiologia
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