Modificación de la prevalencia de genotipos del virus del papiloma humano en los condilomas acuminados tras la instauración de la vacuna profiláctica / Changes in the Prevalence of Human Papillomavirus Genotypes in Genital Warts Since the Introduction of Prophylactic Vaccines

Introducción El condiloma acuminado está causado por el virus del papiloma humano (VPH), cuyos genotipos se han descrito tradicionalmente como de bajo y alto riesgo (AR) oncogénico. Clásicamente, los genotipos más frecuentes son el 6, el 11, el 16 y el 18, incluidos en las dos primeras vacunas desarrolladas. Nuestro objetivo es valorar cambios en la prevalencia de estos genotipos tras 10 años desde la instauración de la vacuna profiláctica en nuestro medio. Material y métodos Se trata de un estudio observacional descriptivo retrospectivo realizado en la UITS de un Servicio de Dermatología entre enero de 2016 y junio de 2019, seleccionando posteriormente a los pacientes diagnosticados de condilomas acuminados. Resultados Se han diagnosticado 362 pacientes con condilomas acuminados, realizándose genotipado en 212 pacientes (58,6%). Se han detectado 32 genotipos distintos, siendo los más frecuentes el 6, el 11, el 16 y el 42. En el 93,9% la detección de VPH fue positiva, detectándose hasta 299 genotipos, lo que corresponde a 1,5 por paciente. En el 26,6% de pacientes se detectaron más de un genotipo distinto de VPH. En el 24,1% se detectó al menos un genotipo de AR. No se observó asociación estadísticamente significativa entre la presencia de un genotipo de AR y las variables estudiadas. En el 91,4% de las lesiones se aisló al menos uno de los cuatro genotipos cubiertos por las dos primeras vacunas desarrolladas. Conclusiones La prevalencia de los genotipos de VPH incluidos en las dos primeras vacunas profilácticas desarrolladas ha disminuido. La implicación de al menos uno de los cuatro genotipos más frecuentes se ha mantenido estable con respecto a hace 10 años. Las infecciones por múltiples genotipos y la presencia de al menos un genotipo de AR oncogénico ha aumentado ligeramente (AU)

Background and objective Genital warts are caused by the human papillomavirus (HPV), whose genotypes have traditionally been classified as low risk or high risk (oncogenic). The first 2 prophylactic vaccines included the most common genotypes at the time: HPV-6, HPV-11, HPV-16, and HPV-18. The aim of this study was to evaluate the prevalence of HPV types in our setting 10 years after the introduction of HPV vaccines. Material and methods Descriptive, observational, retrospective study of patients diagnosed with genital warts at the sexually transmitted infection unit of a dermatology department between January 2016 and June 2019. Results In total, 362 patients were diagnosed with genital warts during the study period, and 212 (58.6%) underwent genotyping. Thirty-two distinct HPV types were observed, the most common being HPV-6, HPV-11, HPV-16, and HPV-42. HPV DNA was detected in 93.9% of the samples analyzed, and there were 299 genotypes (mean, 1.5 per patient). Overall, 26.6% of patients had more than a single HPV genotype, while 24.1% had at least 1 high-risk type. No significant associations were found between the presence of high-risk HPV types and any of the study variables. At least 2 of the 4 HPV types targeted in the original vaccines were detected in 94.1% of lesions. Conclusions Compared to 10 years ago, the prevalences of HPV types included in the first 2 prophylactic vaccines have decreased, while the proportion of patients with at least 1 of the 4 most common types has remained unchanged. We also observed a slight increase in infections with multiple HPV types or at least 1 high-risk type (AU)

[Translated article] Changes in the Prevalence of Human Papillomavirus Genotypes in Genital Warts Since the Introduction of Prophylactic Vaccines / Modificación de la prevalencia de genotipos del virus del papiloma humano en los condilomas acuminados tras la instauración de la vacuna profiláctica

Background and objective Genital warts are caused by the human papillomavirus (HPV), whose genotypes have traditionally been classified as low risk or high risk (oncogenic). The first 2 prophylactic vaccines included the most common genotypes at the time: HPV-6, HPV-11, HPV-16, and HPV-18. The aim of this study was to evaluate the prevalence of HPV types in our setting 10 years after the introduction of HPV vaccines. Material and methods Descriptive, observational, retrospective study of patients diagnosed with genital warts at the sexually transmitted infection unit of a dermatology department between January 2016 and June 2019. Results In total, 362 patients were diagnosed with genital warts during the study period, and 212 (58.6%) underwent genotyping. Thirty-two distinct HPV types were observed, the most common being HPV-6, HPV-11, HPV-16, and HPV-42. HPV DNA was detected in 93.9% of the samples analyzed, and there were 299 genotypes (mean, 1.5 per patient). Overall, 26.6% of patients had more than a single HPV genotype, while 24.1% had at least 1 high-risk type. No significant associations were found between the presence of high-risk HPV types and any of the study variables. At least 2 of the 4 HPV types targeted in the original vaccines were detected in 94.1% of lesions. Conclusions Compared to 10 years ago, the prevalences of HPV types included in the first 2 prophylactic vaccines have decreased, while the proportion of patients with at least 1 of the 4 most common types has remained unchanged. We also observed a slight increase in infections with multiple HPV types or at least 1 high-risk type (AU)

Introducción El condiloma acuminado está causado por el virus del papiloma humano (VPH), cuyos genotipos se han descrito tradicionalmente como de bajo y alto riesgo (AR) oncogénico. Clásicamente, los genotipos más frecuentes son el 6, el 11, el 16 y el 18, incluidos en las dos primeras vacunas desarrolladas. Nuestro objetivo es valorar cambios en la prevalencia de estos genotipos tras 10 años desde la instauración de la vacuna profiláctica en nuestro medio. Material y métodos Se trata de un estudio observacional descriptivo retrospectivo realizado en la UITS de un Servicio de Dermatología entre enero de 2016 y junio de 2019, seleccionando posteriormente a los pacientes diagnosticados de condilomas acuminados. Resultados Se han diagnosticado 362 pacientes con condilomas acuminados, realizándose genotipado en 212 pacientes (58,6%). Se han detectado 32 genotipos distintos, siendo los más frecuentes el 6, el 11, el 16 y el 42. En el 93,9% la detección de VPH fue positiva, detectándose hasta 299 genotipos, lo que corresponde a 1,5 por paciente. En el 26,6% de pacientes se detectaron más de un genotipo distinto de VPH. En el 24,1% se detectó al menos un genotipo de AR. No se observó asociación estadísticamente significativa entre la presencia de un genotipo de AR y las variables estudiadas. En el 91,4% de las lesiones se aisló al menos uno de los cuatro genotipos cubiertos por las dos primeras vacunas desarrolladas. Conclusiones La prevalencia de los genotipos de VPH incluidos en las dos primeras vacunas profilácticas desarrolladas ha disminuido. La implicación de al menos uno de los cuatro genotipos más frecuentes se ha mantenido estable con respecto a hace 10 años. Las infecciones por múltiples genotipos y la presencia de al menos un genotipo de AR oncogénico ha aumentado ligeramente (AU)

Changes in the Prevalence of Human Papillomavirus Genotypes in Genital Warts Since the Introduction of Prophylactic Vaccines. / Modificación de la prevalencia de genotipos del virus del papiloma humano en los condilomas acuminados tras la instauración de la vacuna profiláctica.

BACKGROUND AND OBJECTIVE: Genital warts are caused by the human papillomavirus (HPV), whose genotypes have traditionally been classified as low risk or high risk (oncogenic). The first 2 prophylactic vaccines included the most common genotypes at the time: HPV-6, HPV-11, HPV-16, and HPV-18. The aim of this study was to evaluate the prevalence of HPV types in our setting 10 years after the introduction of HPV vaccines. MATERIAL AND METHODS: Descriptive, observational, retrospective study of patients diagnosed with genital warts at the sexually transmitted infection unit of a dermatology department between January 2016 and June 2019. RESULTS: In total, 362 patients were diagnosed with genital warts during the study period, and 212 (58.6%) underwent genotyping. Thirty-two distinct HPV types were observed, the most common being HPV-6, HPV-11, HPV-16, and HPV-42. HPV DNA was detected in 93.9% of the samples analyzed, and there were 299 genotypes (mean, 1.5 per patient). Overall, 26.6% of patients had more than a single HPV genotype, while 24.1% had at least 1 high-risk type. No significant associations were found between the presence of high-risk HPV types and any of the study variables. At least 2 of the 4 HPV types targeted in the original vaccines were detected in 94.1% of lesions. CONCLUSIONS: Compared to 10 years ago, the prevalences of HPV types included in the first 2 prophylactic vaccines have decreased, while the proportion of patients with at least 1 of the 4 most common types has remained unchanged. We also observed a slight increase in infections with multiple HPV types or at least 1 high-risk type.

Comparison of Phototherapy in Pediatric and Adult Patients. / Experiencia en el uso de fototerapia en pacientes pediátricos y comparación de esta técnica frente a pacientes adultos.

INTRODUCTION: Phototherapy involves the use of UV radiation to treat different dermatologic diseases. Its efficacy and safety have been thoroughly established in adults and some publications indicate that it is also an effective and safe treatment in pediatric patients with refractory skin diseases. MATERIAL AND METHODS: Retrospective study that included all patients under 17 years of age and 122 randomly selected adults who received phototherapy in our department between 2002 and 2017. RESULTS: Ninety-eight pediatric patients (61% girls and 39% boys) with a mean age of 10.5 years received phototherapy. The 3 most frequently treated diseases were psoriasis (48% of patients), vitiligo (17%), and atopic dermatitis (16%). Eighty-six percent of the patients received phototherapy with narrowband UV-B, whereas 7% received phototherapy with psoralen and UV-A (PUVA). No statistically significant differences were found in terms of dosage, duration, or number of sessions compared to the adult population treated with narrowband UV-B therapy or PUVA. A complete response was achieved in 35% of the pediatric patients and no differences were found with respect to the adults. Only 16% of the children showed adverse effects, mostly in the form of mild erythema. We found greater adherence to treatment in the pediatric patients than in the adult patients (P<.05). CONCLUSIONS: Narrowband UV-B therapy and PUVA appear to be safe and effective in children and can be administered using the same treatment protocols as those used in adults. Adherence to treatment is greater in children than in adult patients.

Genital Infection With Herpes Simplex Virus Type 1 and Type 2 in Valencia, Spain: A Retrospective Observational Study. / Infecciones genitales por virus herpes tipo 1 y virus herpes tipo 2 en Valencia, España: estudio observacional retrospectivo.

INTRODUCTION AND OBJECTIVE: The epidemiology of genital herpes has changed in recent years with an increase in the incidence of herpes simplex virus type 1 (HSV-1) infection. The aim of this study was to analyze the clinical and epidemiological characteristics of patients diagnosed with genital herpes. MATERIAL AND METHODS: A retrospective observational study was designed. All patients diagnosed with genital herpes between January 2016 and January 2019 in a Sexually Transmitted Infections Unit (ITS) in Valencia, Spain, were included. RESULTS: We identified 895 STI diagnoses. Of these, 126 (14%) were genital herpes; 68 (54%) of these cases were in women and 58 (46%) in men. Diagnosis was confirmed by molecular detection of HSV DNA in 110 cases (87.3%). Of these, 52 were cases of HSV-1 infection (47.3%) and 58 were HSV-2 infection (52.7%). HSV-2 was more common in men (69.5%), while HSV-1 was more common in women (59.3%). In the subgroup of women, mean age at diagnosis was 26 years for HSV-1 and 34 years for HSV-2 (P=.015). Recurrent genital herpes rates were 13% for HSV-1 and 40% for HSV-2. CONCLUSIONS: There has been an increase in the number of cases of genital herpes caused by HSV-1 in our setting, with young women in particular being affected. This has important prognostic implications because genital herpes caused by HSV-1 is less likely to recur.

Association Between Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Retrospective Cohort Study. / Asociación entre penfigoide ampolloso e inhibidores de la dipeptidilpeptidasa-4: estudio de cohortes retrospectivo.

BACKGROUND: The association between dipeptidyl peptidase 4 inhibitors (DPP-4i) and bullous pemphigoid (BP) has been demonstrated in several studies. The main aim of this study was to estimate the use of DPP-4i treatment in patients diagnosed with BP in our setting. METHODS: We selected patients histologically diagnosed with BP in our department between October 2015 and October 2018 and performed a retrospective chart review to assess clinical and epidemiological data and direct immunofluorescence (DIF) patterns. RESULTS: Of the 70 patients diagnosed with BP during the study period, 50% were diabetic and 88.57% of these were being treated with a DPP-4i when diagnosed with BP. The most common DPP-4i was linagliptin (used in 18.6% of patients), followed by vildagliptin (17.1%). The median latency period between initiation of DPP-4i treatment and diagnosis of BP was 27.5 months for all treatments, 16 months for linagliptin, and 39 months for vildagliptin (log rank < 0.01). A negative DIF result was significantly more common in patients not being treated with a DPP-4i. The DIF pattern most strongly (and significantly) associated with DPP-4i treatment was linear immunoglobulin G deposits along the dermal-epidermal junction. DPP-4i treatment was withdrawn in 87% of patients and 96% of these achieved a complete response. CONCLUSIONS: DPP-4i treatment is very common in patients with BP in our setting. The latency period between start of treatment and onset of BP seems to be shorter with linagliptin than with other types of gliptins. Patients receiving DPP-4i treatment may show different DIF patterns to those not receiving treatment.

Efficacy and Safety of Ixekizumab in a Real-Life Practice: A Retrospective Bicentric Study. / Eficacia y seguridad de ixekizumab en la práctica clínica habitual: estudio retrospectivo bicéntrico.

BACKGROUND: Ixekizumab has proven efficacy and safety for the treatment of psoriasis in clinical trials. The aim of this study was to evaluate its effectiveness and safety in routine clinical practice. METHODS: Retrospective study of all patients treated with ixekizumab in 2 dermatology departments in the city of Valencia, Spain. RESULTS: Seventy-five patients (53.3% men and 46.7% women) with a mean age of 48.61 years were studied; 77.3% (n = 58) had plaque psoriasis and 22.7% (n = 17) had psoriasis predominantly affecting a specific area. The most common comorbidity was obesity (present in 48% of patients) and 40% of the overall group had not been previously treated with a biologic drug. Mean psoriasis area and severity index (PASI) fell from 9.99 at baseline to 1.5 at week 16. PASI-75 and PASI-90 (improvements of at least 75% and 90% in PASI) were independent of sex, age, baseline PASI, and the comorbidities analyzed. Responses at week 16 and 52 were significantly better in biologic-naïve patients for the overall group and the subgroup of patients with localized psoriasis. Adverse effects were reported for 25.7% of patients and the most common effect was injection-site reaction. There were no serious adverse effects. CONCLUSIONS: Our findings show that ixekizumab is both effective and safe in the treatment of psoriasis in routine clinical practice.

Haemophilus Species Isolated in Urethral Exudates as a Possible Causative Agent in Acute Urethritis: A Study of 38 Cases. / Aislamiento de Haemophilus spp. en exudados uretrales como posible agente etiológico de uretritis aguda: estudio de 38 casos.

INTRODUCTION: The incidence of urethritis due to Haemophilus species is increasing. The main aim of this study was to describe the clinical and microbiological characteristics of patients with this form of urethritis. A secondary aim was to discuss the adequacy of treatments in patients with different types of antibiotic resistance. MATERIAL AND METHODS: We studied patients with a microbiologically confirmed diagnosis of urethritis seen at the Sexually Transmitted Infections Unit of our hospital between July 2015 and July 2018. We selected all patients in whom Haemophilus species were isolated on chocolate agar. Antibiotic resistance was tested using the disk-diffusion method. Cross-sectional data were collected prospectively during outpatient visits. RESULTS: Haemophilus species were isolated in 33.6% of cases. The most common clinical manifestation was urethral discharge (57.6%); 60% of the patients were men who have sex with men and in this subgroup Haemophilus species were significantly more common than either Neisseria or Chlamydia species. Haemophilus species were found in isolation in 39.5% of patients and the most common one was Haemophilus parainfluenzae (isolated in 84.2% of cases). In total, 34.2% of patients were resistant to azithromycin and 26.3% were resistant to both azithromycin and tetracycline. Empirical treatment achieved clinical and microbiologic cure in 11 of the patients who were not lost to follow-up (n=17; 44.7%). The remaining 6 patients required treatment with a new antibiotic. CONCLUSIONS: Haemophilus species are a new cause of nongonococcal urethritis, whose incidence is rising, particularly in men who have sex with men who engage in unprotected oral sex. The clinical manifestations are similar to those seen in gonococcal urethritis. Eradication of infection must be confirmed due to the high rate of antibiotic resistance associated with Haemophilus species.

Role of Magnetic Resonance Image in Children with Lumbosacral and Perineal Hemangiomas: Case Reports and Review of the Literature. / Papel de la resonancia magnética en niños con hemangiomas lumbosacros y perineales: informe de 3casos clínicos y revisión de la literatura.

Cutaneous hemangiomas are the most frequent benign tumors in children. When they affect the lumbar and perineal area some cases can be associated with an occult spinal dysraphism. The management of these hemangiomas lack consensus. We report 3 cases of children with lumbosacral and perineal hemangiomas with magnetic resonance image abnormalities and we review the literature to find out the type and timing of tests that should be performed to complete the study in these patients. Ultrasound is typically requested as young as possible, as this imaging technique is not possible 11the posterior spinal elements have ossified. MRI is the gold standard for diagnosing occult spinal dysraphism. According to the literature, the mean age for MRI screening should be around 6 months, when the fat formation in the filum terminale is expanded. In our opinion, an MRI scan should be performed at 6 months of age in every children with lumbar or perineal hemangioma regardless the lesion size, neurological symptoms or the ultrasound results.

Photocarcinogenic Risk Associated With Narrowband UV-B Phototherapy: An Epidemiologic Study in a Tertiary Care Hospital. / Riesgo de fotocarcinogénesis asociado a la fototerapia UVB-BE. Estudio epidemiológico de un hospital terciario.

BACKGROUND: The risk of skin cancer in patients treated with narrowband (NB) UV-B phototherapy is not well understood. Although experimental studies have shown that there is a risk, clinical studies have not detected an increased incidence of cancer following treatment. The aim of this study was to determine the incidence of nonmelanoma skin cancer (NMSC) in patients treated with NB UV-B phototherapy at a tertiary care hospital in the Mediterranean area. MATERIAL AND METHODS: We conducted a retrospective chart review of 474 patients who received whole-body NB UV-B phototherapy at our hospital between 2002 and 2016 and identified those diagnosed with NMSC during follow-up. We calculated the corresponding crude and standardized incidence rates and compared these with rates in the general population in a similar geographic area. RESULTS: Of the 474 patients, 193 (40.7%) were men and 281 (59.3%) were women. The mean (SD) follow-up period was 5.8 (3) years. The prevalence of NMSC at the end of the study period was 1.9% and the standardized incidence was 108.3 cases per 100 000 patient-years. The SIR of 1.9 in the study group was not significantly different from that of the general population. The number of patients who needed to be treated with NB UV-B phototherapy for 1 case of NMSC to occur was 1900. CONCLUSION: NB UV-B phototherapy does not appear to be associated with an increased risk of NMSC.

Adult Xanthogranulomatous Disease of the Orbit: Clinical Presentations, Evaluation, and Management. / Enfermedad xantogranulomatosa orbitaria del adulto. Formas clínicas, evaluación y manejo.

Adult xanthogranulomatous disease of the orbit refers to a heterogeneous group of clinical syndromes with differing degrees of systemic involvement and distinct prognoses. The different syndromes all present clinically with progressively enlarging, yellowish lesions of the orbit. Histologically, the lesions are characterized by an inflammatory infiltrate of foam cells and Touton-type multinucleated giant cells. The xanthomatized histiocytes are CD68+, S100-, and CD1a-. There are 4 clinical forms of xanthogranulomatous disease of the orbit: adult xanthogranulomatous disease of the orbit, adult onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, and Erdheim-Chester disease. The treatment of local lesions are treated with systemic corticosteroids and other immunosuppressors. Vemurafenib, tocilizumab, and sirolimus have shown promising results in systemic disease.

Pediatric Allergic Contact Dermatitis: Clinical and Epidemiological Study in a Tertiary Hospital. / Dermatitis alérgica de contacto pediátrica. Estudio clínico-epidemiológico en un hospital terciario.

BACKGROUND: Few epidemiological studies have investigated the incidence of allergic contact dermatitis in children. Underdiagnosis has been observed in some studies, with many cases in which the condition is not suspected clinically and patch tests are not performed. However, the prevalence of pediatric sensitization to allergens has been reported to be as high as 20%, and the diagnosis should therefore be contemplated as a possibility in this age group. MATERIAL AND METHODS: We performed a retrospective analysis of the skin allergy database of the Dermatology Department of Consorcio Hospital General Universitario de Valencia. Children between 0 and 16 years of age diagnosed with allergic contact dermatitis in the previous 15 years (between 2000 and 2015) were included in the analysis. Epidemiological (age, sex, history of atopy) and clinical (site of the lesions, allergen series applied, positive reactions, and their relevance) variables were gathered. RESULTS: Patch tests had been performed on 4,593 patients during the study period. Of these, 265 (6%) were children aged between 0 and 16 years. A positive reaction to at least one of the allergens tested was observed in 144 (54.3%) patients in that group. The allergens most frequently identified were the following (in decreasing order of frequency): thiomersal, cobalt chloride, colophony, paraphenylenediamine, potassium dichromate, mercury, and nickel. The sensitization was considered relevant in 177 (61.3%) cases. CONCLUSIONS: More than half of the children studied showed sensitization to 1 or more allergens, with a high percentage of relevant sensitizations. All children with a clinical suspicion of allergic contact dermatitis should be referred for patch testing. As no standardized test series have been developed for this age group, a high level of clinical suspicion and knowledge of the allergens most commonly involved are required when selecting the allergens to be tested.

Treatment of Bowen Disease With Photodynamic Therapy and the Advantages of Sequential Topical Imiquimod. / Tratamiento de la enfermedad de Bowen con terapia fotodinámica y ventajas de la aplicación secuencial de imiquimod tópico.

Photodynamic therapy (PDT) has been shown to be useful and effective in the treatment of actinic keratosis, Bowen disease, and basal cell carcinoma. We present a series of 13 Bowen disease lesions treated using PDT. Complete responses were achieved in 11 (84%) of the lesions after 3 months of treatment; at 18 months, complete responses were seen in 9 (70%) of the lesions. Patients who presented a partial response or recurrence were treated with topical 5% imiquimod and achieved complete responses. The lesions that presented partial response or recurrence were the largest lesions, between 3 and 5cm in diameter. PDT in monotherapy or combined sequentially with imiquimod is an excellent and well-tolerated therapeutic option for Bowen disease. The treatment has few adverse effects and shows satisfactory results, particularly in multiple large lesions in areas of difficult surgical reconstruction or in elderly patients with a high surgical risk.

Tratamiento endovascular de la isquemia mesentérica. Revisión y puesta al día / Endovascular treatment of the mesenteric ischemia

La isquemia mesentérica continúa representando una enfermedad con elevada morbimortalidad a pesar de los recientes avances que han mejorado los resultados de la mayoría de las patologías quirúrgicas en las últimas décadas. La cirugía abierta ha sido considerada el tratamiento de elección durante las últimas décadas, pero el intenso desarrollo del tratamiento endovascular durante los últimos años ha facilitado su instauración en gran parte de los centros hospitalarios. Revisamos las generalidades, indicaciones y resultados de los procedimientos endovasculares en el tratamiento de la isquemia mesentérica aguda y crónica (AU)

Mesenteric ischemia continues to be a disease with high mortality despite recent advances that have improved the results of most surgical pathologies in recent decades. Open surgery has been considered the treatment of choice during the last decades, but the intense development of endovascular treatment in recent years has facilitated its establishment in most of the hospitals. We review the general indications and results of endovascular procedures in the treatment of acute and chronic mesenteric ischemia (AU)

[Contiguous gene deletion syndrome in Xp21: an unusual form of presentation]. / Síndrome de deleción de genes contiguos en Xp21: una forma inusual de presentación.

INTRODUCTION: We report a case of an infant where the association of Duchenne's muscular dystrophy (DMD) and pseudohypertriglyceridaemia led to the diagnosis of contiguous gene deletion syndrome in Xp21. CASE REPORT: A 7-month-old male infant who was referred due to psychomotor retardation. The examination revealed pronounced axial hypotonia. Lab findings showed high levels of muscular enzymes with creatine phosphokinase levels of 12,829 IU/L, together with high blood levels of triglycerides. Electromyogram findings were consistent with myopathic compromise. The genetic study for dystrophinopathies revealed the existence of a deletion in the dystrophin gene. Further lab findings identified high glycerol concentrations both in blood and in urine that were compatible with a glycerol kinase deficiency. The genetic study confirmed the existence of a deletion in Xp21 of the genes responsible for DMD, the glycerol kinase deficiency, the congenital adrenal hypoplasia (gene DAX1) and mental retardation (gene IL1RAPL1). CONCLUSIONS: In infants and small children with myopathic compromise, increased levels of creatine phosphokinase and pseudohypertriglyceridaemia it is essential to take into account contiguous gene deletion syndrome in Xp21 to be able to prevent and treat the metabolic complications arising from adrenal hypoplasia.

Gadd45a acts as a modifier locus for lymphoblastic lymphoma.

GADD:45a-/- and p53-/- mice and cells derived from them share similar phenotypes, most notably genomic instability. However, p53-/- mice rapidly develop a variety of neoplasms, while Gadd45a-/- mice do not. The two proteins are involved in a regulatory feedback loop, whereby each can increase the expression or activity of the other, suggesting that common phenotypes might result from similar molecular mechanisms. Mice lacking both genes were generated to address this issue. Gadd45a-/-p53-/- mice developed tumors with a latency similar to that of tumor-prone p53-/- mice. However, while p53-/- mice developed a variety of tumor types, nearly all Gadd45a-/-p53-/- mice developed lymphoblastic lymphoma (LBL), often accompanied by mediastinal masses as is common in human patients with this tumor type. Deletion of Gadd45a in leukemia/lymphoma-prone AKR mice decreased the latency for LBL. These results indicate that Gadd45a may act as modifier locus for T-cell LBL, whereby deletion of Gadd45a enhances development of this tumor type in susceptible mice. Gadd45a is localized to 1p31.1, and 1p abnormalities have been described in T-cell lymphomas. Related human tumor samples did not show Gadd45a deletion or mutation, although changes in expression could not be ruled out.

[Microsatellite analysis in exfoliated cells from urinary sediment. Its utility for the detection of bladder cancer. Comparison with urinary cytology]. / Análisis de microsatélites en células exfoliadas del sedimento urinario. Su utilidad para la detección del cáncer vesical. Estudio comparativo con citología urinaria.

INTRODUCTION: Taking into account the precocity of the genetic alterations in the carcinogenesis of the bladder tumors, the valuation of these changes at a level of 9p 21-22 by means of microsatellite markers could be useful for the diagnostic and follow-up. PURPOSE: To evaluate the use of microsatellite markers and the utility of loss of heterozigosity (LOH) and microsatellite instability (MSI) in exfoliated cells from urine sediment. This observation offers the possibility of tumor detection by examining the DNA of urinary sediment. MATERIALS AND METHODS: We amplified with PCR the DNA of urine and blood samples from 160 patients with bladder cancer. We analysed LOH/MSI in cells from urinary sediment using four microsatellite markers of 9p 21-22 (D9S747-D9S171-D9S162-IFNA) and one from chromosome 4 (D4S243). The urinary cytology was used as comparative method and histological examination of tissue obtained by transurethral resection (TUR) as reference diagnostic. We calculated the sensitivity and specificity of this method and if there was some correlation between stage and grade tumoral. RESULTS: We could use 150 samples correctly. In 111 samples we found LOH/MSI (sensitivity 74%). The cytology was positive only in 60 patients (sensitivity 40%). We found a bigger number of microsatellite alterations (AM) in superficial tumors (sensibility 77.3% vs. 28.8% for the cytology) and these were significant when comparing tumors GI-II vs. GIII (MSI p < 0.001--LOH p < 0.004). The marker with more sensibility was D4S243 with 40%. One patient with prostate carcinoma and another one with chronic cystitis gave false positive results. CONCLUSIONS: The study of LOH/MSI in bladder tumors with 5 microsatellites markers, according to our results showed a sensibility of 74%. The biggest number in LOH/MSI was found in superficial tumors and GI-GII tumors. Although we cannot discard the cystoscopy study in the diagnostic and follow-up, the sensitivity of the urine cytology is better and could be one alternative diagnostic as a non-invasive procedure.

Effect of spermine on the activity of synaptosomal plasma membrane Ca(2+)-ATPase reconstituted in neutral or acidic phospholipids.

The activity of purified plasma membrane Ca(2+)-ATPase (PMCA) from pig brain was inhibited by spermine (a naturally occurring and highly abundant polycation in brain). The level of inhibition was dependent on the phospholipid used for reconstitution as well as on the intact or truncated state of the enzyme. An IC(50) value of 12.5 mM spermine was obtained for both, the intact protein plus calmodulin and the trypsin-digested protein, reconstituted in phosphatidylcholine (PC). In the absence of calmodulin the intact Ca(2+)-ATPase gave an IC(50) of 27 mM. This form was more sensitive to spermine inhibition when it was reconstituted with phosphatidylserine (PS), showing an IC(50) value of 2.5 mM spermine. However, the truncated form was less responsive to spermine inhibition, having an IC(50) value of 12.5 mM. Spermine has no effect on the affinity of the PMCA for Ca(2+) or ATP, but its effect on the protein is pH-dependent. It is suggested that spermine could bind to negatively charged residues on the ATPase with different accessibility, depending on the structural rearrangement of the protein. Further, when the protein is reconstituted in PS, spermine also binds to the lipid.

[Microsatellite analysis of the 3p13-p25 region in renal cell carcinoma in humans]. / Análisis de microsatélites de la región 3p13-p25 en el carcinoma de células renales en humanos.

INTRODUCTION & OBJECTIVES: Interstitial and terminal deletions of different regions of the chromosome 3 have been associated with the development of human nonpapillary renal cell carcinomas. We performed a microsatellite analysis at the region 3p13-p25 to study the role of the short arm of chromosome 3 in the pathogenesis of Renal Cell Carcinomas. MATERIAL & METHODS: Renal tumor specimens and normal kidney tissue from 57 patients were obtained after radical nephrectomy and immediately snap-frozen. Blood samples were also obtained from each patient, immediately processsed and used as normal DNA. To detect allelic loss, we used 8 microsatellite markers covering the region 3p13-p25. Genetic alterations have been correlated with histology, nuclear grade, pathological stage and stromal cell infiltration. RESULTS: A total of 41 cases (71.9%) were clear cell renal cell carcinomas (CCRCC), 7 (12.3%) were chromophobe renal cell carcinomas, 5 (8.8%) were papillary renal cell carcinomas, and 4 (7%) oncocytic tumors. Microsatellite analysis showed loss of heterozigosity (LOH) in 73.2% of the CCRCCs, and in none of the remaining histologic types. Terminal deletions were detected in 53.3% of the nonpapillary RCCs with LOH, and the remaining nonpapillary RCCs showed multiple interstitial deletions (46.6%). A common region of deletion in 3p14.2 has been observed. Due to contamination with normal DNA, when stromal cell infiltration increases, less losses of heterozigosity are detected. We did not find a correlation between LOH at 3p and the nuclear grade, nor between LOH at 3p and the pathological stage. CONCLUSIONS: 1. Microsatellite analysis of LOH at 3p can be used for the differential diagnosis of renal tumors. 2. The evidence of multiple interstitial deletions in a great number of nonpapillary RCCs suggests that more than one gene should be involved in the development of nonpapillary RCC, and already present in early stages of oncogenesis. 3. The common region of deletion 3p14.2 suggests the presence of unstable sequences of DNA that play an important role in the pathogenesis of nonpapillary RCC. 4. LOH at 3p in most nonpapillary RCCs irrespective of the grade and stage, proves that these molecular alterations do not mark a more aggressive behaviour of the tumor.