[Premalignant lesions of the penis]. / Lesiones premalignas del pene.

The dermatological conditions that affect the penis are diverse, and may be typical of this area or be part of systemic diseases. The anamnesis and inspection are often sufficient for diagnosis, but other times, it is difficult to distinguish between benign dermatoses and premalignant lesions. The delay in consulting, due to fear, shame or the doctor's own ignorance, can cause the lesions to progress to malignancy and require aggressive treatments that can alter the quality of life and physical and mental health of the patient. We must suspect premalignancy or malignancy any lesion of the penis that is not modified with specific or empirical treatment and refer for biopsy. HPV infections are the origin of 50% of premalignant lesions. After treatment and due to possible relapses and progression to infiltrating carcinomas, a strict follow-up plan is necessary.

mtDNA haplogroups and osteoarthritis in different geographic populations.

OBJECTIVE: To compare the frequency distribution of the mtDNA haplogroups in OA patients and healthy controls between the United Kingdom (UK) and Spain. METHODS: We used the single base extension (SBE) assay to obtain the European mtDNA haplogroups in 1471 OA patients and 406 healthy controls from Spain, and 453 OA patients and 280 healthy controls from the UK. Some differential haplogroup J-related single nucleotide polymorphisms (SNPs) between both populations were analyzed. The whole data was analyzed with SPSS software (v.18) following appropriate approaches that included chi-square contingency tables and logistic regression models adjusting by gender and age. RESULTS: The haplogroup J appeared underrepresented in OA patients from Spain when compared with healthy controls (OR=0.636; 95% CI: 0.444-0.911; p=0.013). Individuals from the UK carrying the haplogroup T showed a decreased risk of OA (OR=0.574; 95% CI: 0.350-0.939; p=0.027). The comparison of the frequency distribution of the haplogroup J between the UK and Spain showed a decreased presence of this haplogroup in healthy controls from the UK when compared with healthy controls from Spain that is in borderline of the statistical significance (p=0.06). The analysis of some haplogroup J-related SNPs in OA patients and healthy controls from Spain and the UK showed that the SNP m.3394t>c appeared underrepresented in the UK cohort (p=0.038). CONCLUSIONS: The proposed mitochondrial uncoupling mechanism derived from the mtDNA haplogroups J and T could be behind their protective role against OA. The different association found in Spain and the UK could reflect the adaptation of the mtDNA haplogroups to different climatic patterns. The genetic composition of the haplogroup J between the UK and Spain seems to be slightly different, being the m.3394t>c SNP one of the differentially expressed haplogroup J-related polymorphisms.

[Boceprevir and telaprevir safety in routine clinical practice]. / Seguridad de boceprevir y telaprevir en la práctica clínica habitual.

PURPOSE: To compare the safety profile of telaprevir (TLV) and boceprevir (BOC) with each other and with those described in clinical trials (CT). MATERIAL AND METHODS: Retrospective multicenter observational study. Variables collected: age, sex, type of patient (naive, nonresponder or recurrent), fibroscan, Hb nadir, neutrophil and platelet count, presence of rash, anorectal discomfort, number of patients treated with erythropoiesis stimulating factors (EPO) and colony stimulating factors granulocyte (G-CSF). RESULTS: BOC vs CT: anemia (56.5% vs. 49%.), Thrombocytopenia (56.5% vs 32%, p = 0.023). neutropenia (17.4% vs. 29.5%). Use of EPO (13% vs 43%;. p = 0.008), pruritus (13% vs. 21.1%), rash (16.1% vs. 8.7%), anorectal discomfort (4.3% vs. 0%, p = 0.0001), dysgeusia (47.8% vs. 37%). TLV vs. CT: anemia (51.2% vs. 32%, p = 0.014), neutropenia (2.3 vs 3.6%), thrombocytopenia (41.9% vs. 27.4%, p = 0.05), pruritus (39.5% vs 47), rash (16.3% vs 55%, P <0.001), anorectal discomfort (39.5% vs 26%), dysgeusia (14% vs. 9.5%). BOC vs TLV: anemia (56.5% vs 51.2%), neutropenia (17.4% vs 2.3%), thrombocytopenia (56.5% vs 41.9%), rash (8.7% vs 16.3%), pruritus (39.5% vs 13%) and anorectal discomfort (4.3% vs 39.5%, P = 0.006), dysgeusia (14% vs 47.8%, P = 0.007), EPO (13% vs. 25.6%). GCSF was used for a patient treated with TLV. CONCLUSIONS: 1. BOC and TLV have shown a worse safety profile for anemia, thrombocytopenia and anorectal discomfort than those described in CT. 2. As in CT, anemia, neutropenia and thrombocytopenia were more common with BOC. Patients treated with TLV experienced more pruritus, rash and anorectal discomfort.

Seguridad de boceprevir y telaprevir en la práctica clínica habitual / Boceprevir and telaprevir safety in routine clinical practice

Objetivo: Comparar el perfil de seguridad telaprevir (TLV) y boceprevir (BOC) entre sí y con lo descrito en ensayos clínicos (EECC).Material y método: Estudio multicéntrico observacional retrospectivo. Variables recogidas: edad, sexo, tipo de paciente (naïve, no respondedor o recidivantes), fibroscan, Hb nadir, recuento de neutrófilos y plaquetas, presencia de exantema, malestar anorrectal, número de pacientes tratados con estimuladores de la eritropoyesis (EPO) y factores estimuladores de colonias de granulocitos (G-CSF).Resultados: BOC vs EECC: anemia (56,5% vs. 49%), trombocitopenia (56,5% vs. 32%; p = 0,023). Neutropenia (17,4% vs. 29,5%).Utilización de EPO (13% vs. 43%; p = 0,008), prurito (13% vs.21,1%), exantema (8,7% vs. 16,1%); molestias anorrectales (4,3%vs. 0%; p = 0,0001), disgeusia (47,8% vs. 37%). TLV vs. EECC: anemia (51,2% vs. 32%; p = 0,014), neutropenia (2,3 vs. 3,6%), trombocitopenia (41,9% vs. 27,4%; p = 0,05), prurito (39,5 vs. 47%),exantema (16,3% vs. 55%; p < 0,001), molestias anorrectales(39,5% vs. 26%). Disgeusia (14% vs. 9,5%). BOC vs. TLV: anemia (56,5% vs. 51,2%), neutropenia (17,4% vs. 2,3%), trombocitopenia (56,5% vs. 41,9%), exantema (8,7% vs. 16,3%), prurito (39,5% vs. 13%) y molestias anorrectales (4,3% vs. 39,5%; p = 0,006), disgeusia (47,8% vs. 14%; p = 0,007) EPO (13% vs.25,6%). G-CSF se utilizó para un paciente tratado con TLV.Conclusiones:1. BOC y TLV han mostrado un perfil de seguridad peor que en los EECC en cuanto a anemia, trombocitopenia y malestar ano-rrectal.2. Al igual que en EECC, anemia, neutropenia y trombocitopenia fueron más frecuentes con BOC. Por otro lado los pacientes tratados con TLV presentaron más prurito, exantema y malestar anorrectal

Purpose: To compare the safety profile of telaprevir (TLV) and boceprevir (BOC) with each other and with those described in clinical trials (CT).Material and methods: Retrospective multicenter observational study. Variables collected: age, sex, type of patient (naive, non responder or recurrent), fibroscan, Hb nadir, neutrophil and platelet count, presence of rash, anorectal discomfort, number of patients treated with erythropoiesis stimulating factors (EPO) and colony stimulating factors granulocyte (G-CSF).Results: BOC vs CT: anemia (56.5% vs. 49%.), Thrombocytopenia(56.5% vs 32%, p = 0.023). neutropenia (17.4% vs. 29.5%). Use of EPO (13% vs 43%;. p = 0.008), pruritus (13% vs. 21.1%), rash(16.1% vs. 8.7%), anorectal discomfort (4.3% vs. 0%, p =0.0001), dysgeusia (47.8% vs. 37%). TLV vs. CT: anemia (51.2%vs. 32%, p = 0.014), neutropenia (2.3 vs 3.6%), thrombocytopenia (41.9% vs. 27.4%, p = 0.05), pruritus (39.5% vs 47), rash(16.3% vs 55%, P <0.001), anorectal discomfort (39.5% vs26%), dysgeusia (14% vs. 9.5%). BOC vs TLV: anemia (56.5% vs51.2%), neutropenia (17.4% vs 2.3%), thrombocytopenia(56.5% vs 41.9%), rash (8.7% vs 16.3%), pruritus (39.5% vs 13%) and anorectal discomfort (4.3% vs 39.5%, P = 0.006), dysgeusia (14% vs 47.8%, P = 0.007), EPO (13% vs. 25.6%). G-CSF was used for a patient treated with TLV.Conclusions:1. BOC and TLV have shown a worse safety profile for anemia, thrombocytopenia and anorectal discomfort than those described in CT.2. As in CT, anemia, neutropenia and thrombocytopenia were more common with BOC. Patients treated with TLV experienced more pruritus, rash and anorectal discomfort

Use of sugarcane molasses "B" as an alternative for ethanol production with wild-type yeast Saccharomyces cerevisiae ITV-01 at high sugar concentrations.

Molasses "B" is a rich co-product of the sugarcane process. It is obtained from the second step of crystallization and is richer in fermentable sugars (50-65%) than the final molasses, with a lower non-sugar solid content (18-33%); this co-product also contains good vitamin and mineral levels. The use of molasses "B" for ethanol production could be a good option for the sugarcane industry when cane sugar prices diminish in the market. In a complex medium like molasses, osmotolerance is a desirable characteristic for ethanol producing strains. The aim of this work was to evaluate the use of molasses "B" for ethanol production using Saccharomyces cerevisiae ITV-01 (a wild-type yeast isolated from sugarcane molasses) using different initial sugar concentrations (70-291 g L(-1)), two inoculum sizes and the addition of nutrients such as yeast extract, urea, and ammonium sulphate to the culture medium. The results obtained showed that the strain was able to grow at 291 g L(-1) total sugars in molasses "B" medium; the addition of nutrients to the culture medium did not produce a statistically significant difference. This yeast exhibits high osmotolerance in this medium, producing high ethanol yields (0.41 g g(-1)). The best conditions for ethanol production were 220 g L(-1) initial total sugars in molasses "B" medium, pH 5.5, using an inoculum size of 6 × 10(6) cell mL(-1); ethanol production was 85 g L(-1), productivity 3.8 g L(-1 )h(-1) with 90% preserved cell viability.

Psychometric properties of the OARSI/OMERACT osteoarthritis pain and functional impairment scales: ICOAP, KOOS-PS and HOOS-PS.

OBJECTIVES: To evaluate the psychometric properties of the OARSI-OMERACT questionnaires in comparison to the existing validated scales. METHODS: Consecutive hip or knee osteoarthritis patients consulting in an orthopedic department were enrolled in the study. Data collected were pain using the Intermittent and Constant Osteoarthritis Pain (ICOAP), a Numeric Rating Scale (NRS), the Western Ontario McMaster Universities' Osteoarthritis Index (WOMAC) pain subscale, the Lequesne pain subscale; functional impairment using the Knee disability and Osteoarthritis Outcome Score-Physical Function Shortform (KOOS-PS), the Hip disability and Osteoarthritis Outcome Score-Physical Function Shortform (HOOS-PS), a NRS, the WOMAC function sub-scale, the Lequesne function subscale. Validity was assessed by calculating the Spearman's correlation coefficient between all the scales. Reliability was assessed in out-patients with stable disease comparing the data collected within 2 weeks using the intra-class correlation coefficient (ICC). Responsiveness was assessed on the data from hospitalised patients prior to and 12 weeks after a total joint replacement (TJR) using the standardised response mean. RESULTS: Three hundred patients (mean age=68 years, females=62%, hip OA=57%) were included. There was a moderate to good correlation between ICOAP, KOOS-PS, HOOS-PS and the WOMAC, NRS and Lequesne scales. Reliability of the ICOAP hip OA HOOS-PS and KOOS-PS was good (ICC range 0.80-0.81) whereas it was moderate for knee ICOAP (ICC=0.65). Responsiveness of the ICOAP, KOOS-PS and HOOS-PS 12 weeks after TJR was comparable to responsiveness of other scales (SRM range: 0.54-1.82). CONCLUSIONS: The psychometric properties of the ICOAP, KOOS-PS and HOOS-PS were comparable to those of the WOMAC, Lequesne and NRS.

Mitochondrial DNA haplogroups and serum levels of proteolytic enzymes in patients with osteoarthritis.

OBJECTIVE: To analyse the influence of mitochondrial DNA haplogroups, as well as the radiographic grade, on serum levels of proteolytic enzymes in patients with osteoarthritis (OA). METHODS: Serum levels of metalloproteinase-1 (MMP-1), MMP-3, MMP-13, myeloperoxidase and cathepsin K were analysed in 73 patients with OA and 77 healthy controls carrying the haplogroups J, U and H, by ELISA. Knee and hip radiographs were classified according to Kellgren and Lawrence (K/L) scoring from grade 0 to grade IV. Non-parametric and multiple regression analyses were performed to test the effects of clinical variables, including gender, age, smoking status, diagnosis, haplogroups and radiological K/L grade on serum levels of these enzymes. RESULTS: A significant influence of the haplogroups on the serum levels of MMP-3 and MMP-13 was detected (p=0.027 and p=0.035, respectively). Patients with OA with haplogroup H showed higher serum levels of MMP-3 than healthy controls. Serum levels of MMP-13 were significantly higher in patients with OA (p<0.001), and carriers of the haplogroup J showed lower levels than H carriers. Besides, levels of MMP-13 were proportionally higher in radiological groups B (K/L grade II and III) and C (K/L grade IV) than in group A (K/L grade 0 and I) (p=0.005). CONCLUSIONS: This study shows that haplogroups have a significant influence on serum levels of MMP-3 and MMP-13. The influence of the haplogroups on serum levels of MMP-3 is clearly dependent on the diagnosis, whereas the influence of the haplogroups on serum levels of MMP-13 is independent of diagnosis.

Role of European mitochondrial DNA haplogroups in the prevalence of hip osteoarthritis in Galicia, Northern Spain.

OBJECTIVE: To analyse the mitochondrial DNA (mtDNA) haplogroups of patients with hip osteoarthritis (OA) and those of healthy controls in a Spanish population. METHODS: mtDNA haplogroups were assigned to 550 cases of hip OA and 505 clinically asymptomatic controls. Sets of controls with healthy knees and hips (n = 179) and patients with knee and/or hip OA (n = 977) were also analysed in a multivariate analysis after adjusting for sex, age and smoking. RESULTS: Individuals carrying haplogroup J showed a significantly decreased risk of developing hip OA (OR 0.661; 95% CI 0.440 to 0.993; p = 0.045). In addition to haplogroup J, smoking protected against the development of hip OA (OR 0.543; 95% CI 0.311 to 0.946; p = 0.031). However, no relationship was found between rheumatoid arthritis and mtDNA haplogroups. CONCLUSION: The results of this study support the hypothesis that the mtDNA haplogroups have a role in the complex osteoarthritic process.

Genetic variation in the nuclear factor kappaB pathway in relation to susceptibility to rheumatoid arthritis.

OBJECTIVE: To examine genetic association between rheumatoid arthritis (RA) and known polymorphisms in core genes of the nuclear factor (NF)kappaB pathway, the major intracellular pathway in RA pathogenesis. METHODS: Discovery and replication sample sets of Spanish patients with RA and controls were studied. A total of 181 single nucleotide polymorphisms (SNPs) uniformly spaced along the genomic sequences of 17 core genes of the NFkappaB pathway (REL, RELA, RELB, NFKB1, NFKB2, NFKBIA, NFKBIB, NFKBIE, IKBKA, IKBKB, IKBKE, IKBKAP, KBRAS1, KBRAS2, MAP3K1, MAP3K14, TAX1BP1) were studied by mass spectrometry analysis complemented with 5'-nuclease fluorescence assays in the discovery set, 458 patients with RA and 657 controls. SNPs showing nominal significant differences were further investigated in the replication set of 1189 patients with RA and 1092 controls. RESULTS: No clear reproducible association was found, although 12 SNPs in IKBKB, IKBKE and REL genes showed significant association in the discovery set. Interestingly, two of the SNPs in the IKBKE gene, weakly associated in the discovery phase, showed a trend to significant association in the replication phase. Pooling both sample sets together, the association with these two SNPs was significant. CONCLUSION: We did not find any major effect among the explored members of the NFkappaB pathway in RA susceptibility. However, it is possible that variation in the IKBKE gene could have a small effect that requires replication in additional studies.

Pre- and post-hatching developmental changes in beta-adrenoceptor subtypes in chick brain.

This study used [3H]CGP 12177 as a radioligand to determine the beta1 and beta2-adrenoceptor changes from the pre-hatching E17 stage, where the beta2 subtype is first detected, to the post-hatching P30 stage. While beta1-adrenoceptors were found to be present from E18 and were limited to cerebellum and hyperstriatum in all stages studied, beta2-adrenoceptors showed a wider distribution throughout the brain. In most of the structures analysed both beta1- and beta2-adrenoceptor binding values reached a maximum in the P2 stage, followed by a decrease over the following days. A second increase in both subtypes was detected again in the P15 and P30 stages. These results support the notion of a specific role for beta-adrenoceptors in neural plasticity in the first week after hatching and suggest that the beta2 subtype is the main adrenoceptor in chick brain throughout its development.