E6/E7 oncogenes in epithelial suprabasal layers and estradiol promote cervical growth and ear regeneration.

Tissue growth is a common characteristic of carcinogenesis and regeneration. Here we show that suprabasal expression of human papillomavirus (HPV)16 E6/E7 oncogenes in Tg(K6b-E6/E7) mice, similar to that observed in HPV-infected human tissue, and estradiol increased cervical epithelium growth and ear-hole closure efficiency. Oncogenes in combination with estradiol had a significant contribution to the proliferation of suprabasal cells of cervical epithelium that correlated with an increased expression of keratin genes. Remarkably, long-term treatments with estradiol resulted in evident cellular and tissue abnormalities indicative of a precancerous phenotype. Regenerating ear epithelium of transgenic mice also showed increased suprabasal cell proliferation and expression of keratin genes. Unexpectedly, we observed higher ear regeneration efficiency in adult than in young female mice, which was further increased by E6/E7 oncogenes. Supporting a role of estradiol in this phenomenon, ovariectomy and treatment with an estrogen receptor inhibitor caused a significant reduction in regenerative capacity. Our data suggest that Tg(K6b-E6/E7) mice are unique to mimic the initial stages of HPV-mediated cervical carcinogenesis, and ear regeneration could facilitate the elucidation of mechanisms involved.

[Cost-effectiveness analysis of patient-controlled analgesia compared to continuous elastomeric pump infusion of tramadol and metamizole]. / Análisis coste-efectividad de la PCA postoperatoria frente a la infusión continua elastomérica de tramadol y metamizol.

OBJECTIVES: Little information is available on the cost-effectiveness of postoperative patient-controlled analgesia (PCA). The present study compared PCA to continuous infusion by elastomeric pump. MATERIAL AND METHODS: Fifty ASA 1 or 2 patients undergoing major gynecologic surgery were enrolled for a randomized controlled trial to evaluate the effectiveness and costs derived from intravenous PCA with metamizole and tramadol compared to continuous infusion of the same analgesic solution by elastomeric pump in the 48 hours following surgery. Patient satisfaction and side effects were also recorded. RESULTS: The analgesic effectiveness and side effects of the 2 regimens were similar, although 61% of patients in the elastomeric pump group needed morphine for rescue analgesia compared to 33% in the PCA group (P < .05). In the PCA group, 81% of the patients said they would repeat the analgesic treatment compared to only 56% in the elastomeric pump group (P = .05). The mean number of nursing interventions was 16 for the PCA group and 19 for the elastomeric pump group. The mean cost of the treatment (not including the PCA pump, provided by the manufacturer) was Euros 41.35 for the PCA group and Euros 56.22 for the elastomeric pump group. CONCLUSIONS: The analgesic efficacy of the 2 regimens was similar. However, patient satisfaction was greater with PCA and use of an elastomeric pump was more expensive. In the setting of the present study, postoperative PCA proved to be more advantageous than continuous elastomeric pump infusion.

Análisis coste-efectividad de la PCA postoperatoria frente a la infusión continua elastomérica de tramadol y metamizol / Cost-effectiveness of patient-controlled analgesia compared to continuous elastomeric pump infusion of tramadol and metamizole

OBJETIVOS: Existen pocos datos relativos al coste-efectividad de los sistemas de analgesia controlada por el paciente (PCA) en el postoperatorio. El presente estudio compara desde esta perspectiva la PCA con una infusión elastomérica continua. MATERIAL Y MÉTODO: Estudio prospectivo, controlado y aleatorizado en 50 pacientes ASA I o II sometidas a cirugía mayor ginecológica, que evalúa durante las primeras 48 horas de postoperatorio la efectividad, los efectos secundarios, la satisfacción y los costes derivados de la administración de una pauta PCA i.v de metamizol y tramadol (Grupo PCA), frente a la infusión elastomérica continua de la misma solución analgésica (Grupo Elastómero). RESULTADOS: La efectividad analgésica y los efectos secundarios de las pautas fueron similares, aunque más pacientes del Grupo Elastómero precisaron rescates analgésicos con morfina (61% frente al 33% del grupo PCA; p < 0,05). El 81% de las pacientes del Grupo PCA repetirían el tratamiento analgésico frente a sólo el 56% del grupo Elastómero -p = 0,05-). El número medio de intervenciones de enfermería fue de 16 y 19 para los grupos PCA y Elastómero respectivamente. Los gastos medios de los tratamientos (no incluida la bomba PCA facilitada por la industria) ascendieron en el grupo PCA a 41,35 euros frente a los 56,22 euros del grupo Elastómero. CONCLUSIONES: Ambas pautas presentaron una eficacia analgésica parecida aunque la PCA resultó más satisfactoria, a la vez que el elastómero fue más caro. En las condiciones particulares de nuestro estudio la PCA postoperatoria resultó más ventajosa que la infusión continua elastomérica (AU)

OBJECTIVES: Little information is available on the cost-effectiveness of postoperative patient-controlled analgesia (PCA). The present study compared PCA to continuous infusion by elastomeric pump. MATERIAL AND METHODS: Fifty ASA 1 or 2 patients undergoing major gynecologic surgery were enrolled for a randomized controlled trial to evaluate the effectiveness and costs derived from intravenous PCA with metamizole and tramadol compared to continuous infusion of the same analgesic solution by elastomeric pump in the 48 hours following surgery. Patient satisfaction and side effects were also recorded. RESULTS: The analgesic effectiveness and side effects of the 2 regimens were similar, although 61% of patients in the elastomeric pump group needed morphine for rescue analgesia compared to 33% in the PCA group (P<.05). In the PCA group, 81% of the patients said they would repeat the analgesic treatment compared to only 56% in the elastomeric pump group (P=.05). The mean number of nursing interventions was 16 for the PCA group and 19 for the elastomeric pump group. The mean cost of the treatment (not including the PCA pump, provided by the manufacturer) was €41.35 for the PCA group and €56.22 for the elastomeric pump group. CONCLUSIONS: The analgesic efficacy of the 2 regimens was similar. However, patient satisfaction was greater with PCA and use of an elastomeric pump was more expensive. In the setting of the present study, postoperative PCA proved to be more advantageous than continuous elastomeric pump infusion (AU)

Diagnostic and treatment of Zenker's diverticulum: review of our series pharyngo-esophageal diverticula.

BACKGROUND/AIMS: Clinical aspects and preneoplastic potential of Zenker's diverticulum justify its surgery. The clinical signs of the patients and the size of the diverticulum determine the surgical technique. METHODOLOGY: Between January 1974 and December 1995, 32 patients underwent surgery in our department. In order to compare the surgical technique, we divided the patients into 3 groups: group A (cricopharyngeus myotomy: 15 patients (46.9%)), group B (myotomy with diverticulectomy: 15 patients (46.9%)) and group C (myotomy with diverticulopexy: 2 patients (6.7%)). The chi-square test was used for statistical analysis, p < 0.05. RESULTS: Local or regional anaesthesia was used in 7 patients from group A (46.6%); 5 patients from group B (33.3%) and all the patients from group C (100%). General anaesthesia was used in 8 patients from group A (53.4%), 10 patients from group B (66.7%) and 0 patients from group C (0%). The overall mortality was 0%. The mean postoperative stay in group A was 6 +/- 2 days (3-10 days); in group B was 11.6 +/- 6.4 days (5-25 days) and in group C was 3.5 +/- 0.7 days (3-4 days). The mean postoperative stay in patients with local or regional anaesthesia was 5.3 +/- 1.6 days (3-9 days) and in patients with general anaesthesia, 10.9 +/- 6.1 days (4-25 days). No statistically significant difference was found between the anaesthetic technique and the surgical technique (p = 0.193), between the surgical technique and the mean postoperative stay (p = 0.596) and between the anaesthetic technique and the mean postoperative stay (p = 0.166). CONCLUSIONS: Cricopharyngeus myotomy is the main surgical technique, however, in diverticula longer than 3 cm of diameter it is mandatory to associate diverticulectomy. Diverticulopexy is indicated in patients of advanced age with a high surgical risk. Local or regional anaesthesia facilitates the identification of the diverticulum intraoperatively and reduce the mean postoperative stay, however, there is no statistical significant difference.

Retinoic acid and methylation cis-regulatory elements control the mouse tissue non-specific alkaline phosphatase gene expression.

To understand the mechanisms regulating the tissue non-specific alkaline phosphatase (TNAP) activity during development, we characterized cis-transcriptional regulatory elements. In embryonic cells and tissues, TNAP expression was driven preferentially by the exon 1A (E1A) promoter, one of the two promoters previously defined. Transcriptional activity of E1A promoter was up-regulated by retinoic acid (RA) through a putative RA-responsive element. Transgenic mice analysis with lacZ reporter constructs revealed negative regulatory elements within 8.5 kb of E1A promoter. Promoter sequences of endogenous TNAP in non-expressing tissues and those carried by the 8.5 kb-lacZ transgene were found to be highly methylated. A 1 kb fragment of E1A promoter increased the methylation level of lacZ and promoter sequences. The role of RA and DNA methylation in defining the embryonic expression pattern of TNAP is discussed.